here is a perfect timing within everything. Within every thought, feeling and action there is a divine alignment to the cycles of the seasons, planets, stars, and galaxies. One cannot hurry the ripening process of a fruit, force a baby to develop faster, nor increase the planet's momentum around our Sun. The planet is moving through space around the Sun at the perfect speed of 67,000 mph. We wouldn't want it to move faster or slower since it would throw everything off balance. We are part of a vast Universe that is carefully orchestrated with the most Divine Perfection. Once we are tuned into this perfection that is already here now, our lives emulate a divine synchronicity everywhere we are.
“The key to everything is patience. You get the chicken by hatching the egg, not by smashing it.” ~ Arnold H. Glasgow
The tomato falls naturally from the vine when it is ripe, and just like you, it naturally knows when to hold on and when to let go. When you learn to live each moment relaxed in your body, you naturally live in divine harmony with the Universe. Your entire energy field opens up and you become receptive to whatever the Universe brings your way. Through deep relaxation there is a sense of acceptance, and a deep feeling of being in alignment with everything. Relaxation is simply practicing, "Being With What Is" whether it's your innermost thoughts about you, or your ideas about the outer world. Through relaxing, you naturally become patient and are in tune with the cosmic timing behind everything and can truly see that the world is perfect just the way it is.
“He that can have Patience, can have what he will” ~Benjamin Franklin
So where does impatience come from? It is an ego based energy that stems from not choosing to be at peace with what is. It's an old habit brought on by not loving yourself, your body, your friends, family, and your experience of this world just the way it is. You tend to push or rush through an experience when love is not present. Rushing is truly an act of violence to your soul. It's all about the ego trying to make the river flow faster because it thinks once it gets through this experience THEN the goodies will arrive and it will finally be happy, rich, fulfilled and at peace. The big joke is that the ego never arrives at peace because it's a wanting machine! As you may have already noticed, your ego wants everything that it wants right now! It is not willing to wait another day. It acts like a spoiled child yelling for Mother to fetch its favorite chocolate. It wants exactly WHAT it wants WHEN it wants it, and not a moment later. It doesn't care whether the season is right, it just NEEDS to be satisfied now or else!
"Misery does not exist in reality but only in mere imagination." ~Ramana Maharshi
By rushing to get things done, your body becomes contracted, your mind narrows and your being misses this divine moment. With all this constriction you block the flow of your Manifesting Vibration, causing things to manifest with massive delay and perhaps never come to fruition. The ego is impatient simply because it feels separate from this divine ocean of existence. This suffering is caused by years of believing in the Great Illusion, that you are not connected to the Infinite Source of love, intelligence, and power. The ego is obsessed with its own private agenda. It has its own "separate" desires, time schedule, and has completely forgotten about merging with God and experiencing bliss. Whenever your ego is in charge, you will rush through each life experie nce and actually miss the greater mission of your life, which is to celebrate your life, and ridiculously enjoy this amazing divine existence.
“Patience is the companion of wisdom.” ~ Saint Augustine
By practicing relaxing into each experience of your life, you will magically increase your Manifesting Vibration and always bring your desires more effortlessly to you. Patience is a major aspect in the process of consciously manifesting what you desire. With infinite patience, you can send any request into the Universe and it will easily manifest! It is important to let go of attachment to your future outcome and patiently allow the Universe to answer your request. The most Divine timing is waiting for you. The question is can you relax enough to wait for it?
“Hurry up...and wait.” ~John Oswald
One of the best ways to master patience is learning how to live in society in a relaxed, open, and receptive body. This means living IN the world, yet not OF the world. Being connected to the big rat race, yet not rushing to get ahead of the other rats. Whenever you are late for an event, instead of rushing and freaking out about what might happen, enjoy the excitement of the journey there. Know that the more you rush, the more impatient energy you are creating. Whenever you "have to" wait for someone, instead of being impatient choose to see that you "get to" wait. This is your opportunity of the day to practice relaxing into your magical manifesting vehicle! What if every time you had to wait, it was actually the Universe offering you this amazing gift to take a mini-vacation and enjoy yourself deepl y! Waiting allows you to deeply sink into a vast spaciousness where you can taste the beauty of your infinite soul. Waiting is really just a form of meditation. Doing nothing means your mind and heart are completely in the now, and not focused on the past or future, and receiving the divine blessings of existence. Be patient and all the goodies you desire will spring forth into existence.
Throughout my recent travels in Uganda to assist the children there, I (Margot) have experienced countless hours of waiting. The Ugandan people have a different relationship with time and are in general very patient. They were my greatest teachers in this arena. I never ceased to marvel at their ability to patiently wait even in uncomfortable situations without complaining or trying to change anything. I experienced eight hour bus rides where people stood in the aisle, some even carrying babies on their backs. It is normal in Uganda to wait for a bus to fill up with people for an hour or so before it even leaves. I invite you to imagine what that would be like to be that patient. There are sooooo many oppor tunities to practice patience, such as sitting in traffic, at stop lights, with children, your partner, or even waiting for the right moment to speak your truth. With each opportunity we invite you to notice how you feel inside as you drop deeper into choosing the experience of being patient.
"Patience and perseverance have a magical effect before which difficulties disappear and obstacles vanish." ~ John Quincy Adams
PATIENCE
Creativity
1.think about creativity
Brainstorm. If properly carried out, brainstorming can help you not only come up with sacks full of new ideas, but can help you decide which is best. Click here for more information on brainstorming.
3.
Always carry a small notebook and a pen or pencil around with you. That way, if you are struck by an idea, you can quickly note it down. Upon rereading your notes, you may discover about 90% of your ideas are daft. Don't worry, that's normal. What's important are the 10% that are brilliant.
4.
If you're stuck for an idea, open a dictionary, randomly select a word and then try to formulate ideas incorporating this word. You'd be surprised how well this works. The concept is based on a simple but little known truth: freedom inhibits creativity. There are nothing like restrictions to get you thinking.
5.
Define your problem. Grab a sheet of paper, electronic notebook, computer or whatever you use to make notes, and define your problem in detail. You'll probably find ideas positively spewing out once you've done this.
6.
If you can't think, go for a walk. A change of atmosphere is good for you and gentle exercise helps shake up the brain cells.
7.
Don't watch TV. Experiments performed by the JPB Creative Laboratory show that watching TV causes your brain to slowly trickle out your ears and/or nose. It's not pretty, but it happens.
8.
Don't do drugs. People on drugs think they are creative. To everyone else, they seem like people on drugs.
9.
Read as much as you can about everything possible. Books exercise your brain, provide inspiration and fill you with information that allows you to make creative connections easily.
10.
Exercise your brain. Brains, like bodies, need exercise to keep fit. If you don't exercise your brain, it will get flabby and useless. Exercise your brain by reading a lot (see above), talking to clever people and disagreeing with people - arguing can be a terrific way to give your brain cells a workout. But note, arguing about politics or film directors is good for you; bickering over who should clean the dishes is not.
NOVELEX(Novel Exercise)
Dr. Arnold Scheibel a neuroscientist beleives firmly that novel tasks stimulate brain power. Challenge the brain with anything new and different. He advises people to do things they have never done before. He himself recently took up sculpture. Novelty is very biologically stimulating to the brain. The Novelex programme calls for providing the brain with novel,unique and different eperiences on a day-to-day basis. They should constitute non-routine and unexpected experiences using various combinations of your physical senses - vision, hearing,taste,smell, and touch. It differs from other types of brian exercise, such as solving puzzles, riddles, magic squares, mathematical/accounting problems and memory exercise. Novelex makes use of the five senses in novel ways to develop the brain's natural drive to form associations between different types of information.
Adults normally go through life in remarkabnly fixed routines.Most of their actions are perfectly predictable and free from surprise.The result is that our brains's ability to make new associations declines. Routine behaviours are almost subconscious in nature and performed using a minimum of brain energy. Thus the brain gets little exercise . The power of the cortex to create new associations is, therfore, not properly utilised. The human brain hungers for novelity. It is designed to repond to new information coming from the outside world. the brain gets stimulated when novel and unexpected stimuli are presented. It is what turns the brain on. In reponse to novelity, cortical activity is increase in more and varied brain areas. this strenghtens synaptic connections, links different areas together in new patterns, and pumps up the production of neurotrophins.
Noveles is neither passive nor routine. It uses the sense in novel ways to break out of everyday routines. The latest brain imaging studies have clearly established that novel tasks activate large of the cortex , indicating increased levels of brain activity in several distinct areas. Of the five senses with which we establish contact with the outside world, we mostly rley upon only the two sense of vision and hearing. the other senses of taste,smell and touch are rarely used. Novelex makes use of all the senses.
Any exercise programme demands time. One should be higly motivated to set aside a specific time to slot take up a physical exercise programme. Fortunately, NOvelex programmes are designed in such a way that they fit into what you do routinely, without taking extra time.
they are recommended as a lifestyle choice, nopt as a crash course or a quick fix. Simply by making small changes in your daily habits you can turn daily routines into 'mind-building' exercise. How ever, Novelex exercises should not become a routine affair.
The following techniques constitute Novelex:
We normally use the sense of vision for most of our routine activities. When the sense of vision is blocked, you are forced to use other senses. For example, get dressed for office with your eyes closed.
If you are right handed , start using your left hand for most routine work like brushing your teeth , buttoning clothes, opening the door ,turning on switches, etc. A variety of things can be done using your left hand. When you use your left hand, your right brain is stimulated, which we rarely stimulate.
When you go on yuour normal route your brain gets on automatic pilot. When anything is done automatically without any awareness, the brain is not stimulate at all.
when you take a new route all your sense must be alert while you drive.
But if you want to stimulate your brain readin aloud helps. You may also ask a friend to read to you. When you read aloud or listen to someone read , you use very different circuits tha when you read silently. Brain imaging clearly showed three distint brain regions lighting up when the same word was read , spoken or heard. for example, listening to words activated two distinct areas in the left and rigth hemispheres of the cortex, while speaking words activated the motor cortex on both sides of the brain as wll as the crebellum. Just looking at words activites only one area of the corted in the left hemisphere.
Do all the Novelex and Find out how refreshing you will be.Home
Stress
Stress destroys the ability to concentrate in several ways:
Manage stress by developing a wholesome philosophy in life:
For effective functioning of the brain it is essentiqal to manage stress by adopting the following philosophy in life:
God, grant me the serenity
To accept the things I cannot change
the courage to change the things I can
And the wisdom to know the difference.
No one is superior to me
No one is inferior to me
I am what I am.
Be convinced that you are something new in this world. Be proud of being unique."Make the most of what Nature gave you. In the last analysis all art is biographical. You can sling only what you are. You must be what your experience,your environment and your heredity have made you. For better or for worse,you must cultivate your own little garden, and play your own little instrument in the orchestra of life," said the Legendary Dale Carnegie.
success or failure is a matter of attitude in life. We should take life as it unfolds. Our main business in life is to involve ourselves deeply in the creative activities in which we are keenly interested without bothering much about reward or result.There is no question of failure. Failure might or result.There is no question of failure .Failure might suggest that we have to make some more attempts to accomplish the task in hand. Develop the attitude:
"When I win I win ,when I lose I learn".Every second of our wakeful state provides a wonderful opportunity to learn one thing or another.Every failure should be considered as deferred success. Never quit.Pursue your project till you succeed in your attempts.
"Never,Never,Never.Never, NEVER GIVE UP" said WINSTON Churchill.
Think in a positive way that whatever happens to you in life is for your own good. An ancient story is related here to illustrate this point:
A king and his minister went into a jungle to hunt. A tiger attacked them and in the fight the king lost a finger. He was in agony, but the minister said,"Every thing is for our good." At this the king got angry and pushed him into a shallow dry well. Falling into the well, the minister uttered,"Everthing is for our good."
After a while some tribals captured the king. They intended to sacrifice him,bu on second thought freed him when they realised he was minus a finger. Then the king came to the minister, rescued him from the well and asked, "Why did you say 'Everthing is for our good' when I pushed you into the well?"
The minister said: "you Majesty was saved because of the loss of a finger, for the sacrificial victim should not have any blemish. But if I had not been pushed into the well, they would have sacrificed me."
one of the best ways to manage stress is to convert minus into plus. Count your blessings and not your troubles. Develop an attitude to convert minus into plus.
There is virtually no justice and fairness in this world. The general trend is that might is right. The prisons are filled only with those who are not able to defend their case with money. People in power do far worse things but escape due to the power they hold.Few politicians in India have been punished for fraudulent and corrupt practices. Only poor and helpless people are regularly punished and victimised. There fore, don't except justice and fairness at every turn of life3.
People may tend to forget the good you have done them. It is unwise to expect that every one should be graceful.
We cannot reason our everything that happens in our life. A certain amount of mystery pervades the life of everyone. In an accident many died and a few escaped. Why? we don't know.Accept it.
This is one of the best principles to be adopted in the sphere of personal growth and development. We should always be satisfied with what we have but not with what we are. It i s better to strive hard to improve our potential , capabilities ,efficiency, character etc. Every minute of our personality for a happy and prosperous life through a stress free attitude.
Kaizen is the word given by the Japanese for continuous steady growth and development in life.
Travel
Visiting new places and interacting with strangers is a good way to coax the brain into making new demdritic connections. What you should mostly avoid is simply doing nothing. Those who remain active perserve cognitive function and brain metabolism. Travel provides abundant opportunity for mental exercises, which is vitally important for brain regeneration.
Right Brain and Left Brain
The three part brain is also divided into a right and left hemisphere. Each hemisphere is responisible for differnt modes of thinking, each specialising in certain skills.
Although there is some crossover and interaction between the two sides, the thinking processes of the left brain are
The right brain thinking modes are
To lead an effective life both hemisphers of the brain should be given equal importance. Those who make use of both hemispheres of the brain tend to produce better results in life. They learn very fast. Most geniuses use both left and right brains . Unfortunaely, the modern sytem of education emphasisesleft brain activities and neglects right brain activities.
Martial Arts for brains development
Marshal arts (also known as kung-fu or Wushu) are one of the typical demonstrations of traditional Chinese culture which includes Wushu and Qu Gong. Perhaps it is one of the earliest and long-lasting sports, which utilizes both brawn and brain. The theory of Wushu id based upon classical Chinese philosophy. Throughout its long history it has developed characteristically with a unique combination of healthy push, practical self-defense, self-discipline and art. In sports such as field and track, ball sports, weightlifting, and boxing, an athlete typically has to retire from full participation in his or her 30s, due to failing physical vigor. The athlete often will have sustained injuries that he r she was not aware of and those injuries will affect his or her health in middle age and older, because of overexertion when young. In Chinese kung-fu, however, a distinction is made between “external” and “internal” kung-fu, it is said that “In external kung-fu, you exercise your tendons, bones, and skins; in internal kung-fu, you train your spirit, your Qi, and your mind.” In addition to training to achieve strong body and mind, strengthen internal organs, and increase circulation of one’s Qi, or flow of vital energy. Progressing from movement to stillness, from firmness to softness, the older one gets the more adept one becomes at kung-fu. And the higher one’s level of achievement in kung-fu, the better one is at maintaining good health and living a long, active life. For Chinese kung-fu, the internal training, that is, practicing Qi Gong, is essential. Chinese say: “Practicing boxing without practicing Qi Gong will come to nothing.”
The skills of Chinese Wushu consist of various forms of fighting: fist fights, weapon fights, and other fighting routines (including such offence and defenses acts as kicking, hitting, throwing, holding, chopping and thrusting) and unarmed combats. According to statistics, there are over 100 schools of Chinese boxing. Among them, seven schools (Shao Lin, Wu Dang, Tai Ji, Xing Yi, Ba Gua, E Mei and Nan Quan) are widely recognized. People see many individual styles within each of these schools.
Yongchun Quan (Eternal Youth Boxing) originated in Fujian Province, later spreading south to Guangdong, Macao hang Hong Kong. Yongchun Quan is just one of a number of styles under the general term, Nan Quan, the Southern Schools of Boxing, a vigorous and aggressive school popular south of the Yangtze River. Of the many styles of Nann Quan, the mists well known are Hongjia Quan, Liujia Quan, Caijia Quan, Lijia Quan, and Mojia Quan, “the Five Great Schools”. Other schools of Nan Quan are Tiger and Crane Boxing, White-Eyebrow Boxing, Confucian Boxing, Souther Skills Boxing, Kunlun Boxing, House of Kong Boxing, Han-Exercising Boxing, Diao School of Teaching, Yue School of Teaching, and Song School of Teaching.
Bei Quan, the Northern School of Boxing is a generic term for those schools in the provinces north of the Yangtze River. Characterized by speed and strength, the Northern School emphasizes variations of kicking and footwork, hence the common saying “Southern fists, Northern legs.” The major styes of the Northern School are Shaolin Boxing, Wheeling Boxing, Zha School of Boxing, Essence Boxing, Flower Boxing, Cannon Boxing, Hong School of Boxing, Full-Arm Boxing, Maze Boxing, Six-Harmony Boxing, Springing Legs, Jabbing Feet, Eigh-Ultimate Boxing, Great Ancestor Extended Boxing and Silk Floss Boxing.
Chinese Wushu involves practice with weapons as well as well as the standard bare-hand skills. Weaponry includes nine kinds of long weapons and nine short, such as knives, spears, swords, and clubs, which together constitute what is called the Eighteen Types of Martial Arts. The majority of these weapons, hence the use of the term the “eighteen military weapons”. This term was already widely used during the Song Dynasty. The Ming novel, Outlaws of the Marsh mentioned it frequently. One version of the book records the eighteen military weapons as the lance, mallet, long bow, crossbow, jingal, jointed bludgeon, truncheon, sword, chain, books, hatchet, dagger-axe, battle-axe, halberd, shield, staff, spear and rake. Today, the term generally refers to the broadsword, lance, rapier, halberd, hatchet, harrow, trident, staff, long-blade spear, cudgel, dagger-axe and wave-bladed spear. This is only a general term, since military weapons were never restricted to just eighteen forms. Other weapons frequently used include the rope-dart, Emei dagger named after the Emei Mountain in Sichuan Province from which the style originated, as well as the bent handled club and hook. Today, the wide variety of weapons used in Wushu practice fall into four groups:
1. Long weapons: Longer than the height of a person and wielded with both hands during practice. They include the lance, staff, great broadsword, spear, halberd, fork, trident and spade.
2. Short weapons: Shorter than the height of a person and wielded with one hand. These include the broadsword, rapier, hatchet, hammer, truncheon, jointed bludgeon, dagger and shield.
3. Soft weapons: Rope, chains, or sings are used to create linked weapons which are able to strike cloae or far and are wielded with one or both hands. They include the nine-sectioned chain, three-sectioned flail, flying hammers, which are tow iron balls linked by a long iron chain, the rope dart, flying claw and the ordinary flail.
4. Twin weapons: Here a pair of weapons are wielded, one in each hand. These include twin broad-swords, handled clubs, twin lances, twin hatchets, twin daggers, double-bladed daggers, Pangusnbi (Twin rods with fist-shaped heads) and duck and drake battle-axes.
Taiji Quan (Tai Chi) originated long age in Chinese history, and was a martial arts practice, with Quan meaning fist or boxing. Due to its heritage and practicability, it has evolved in three directions. With its origin and heritage in Taoism, it is a way to spiritual perfection; with its practicability, it is a way to protect oneself or really fight; and with its health caring effects, it is accepted by the common people as a self-healing or disease prevention or treatment tool.
Taiji Quan boasts several major school of Yang Style, Chen Style, Wu Style, and Sun style, etc., which in turn include a variety of forms respectively. For instance, the Yang school includes the Greater Routine and the Lesser Routine, while the Chen School includes an Old Routine, a New Routine, and the Zhaobao Routine. And most of these forms have created a short form, with Yang Style of 48 movements as an example. Therefore, the beginners are able to learn it more quickly, and the elder or patients are able to learn it more easily.
Tianji Quan exercises are believed to be helpful in treating illness and strengthening the constitution, therefore it is an exercise performed regularly by many people to keep fit, prevent and cure diseases, slow down the pace of growing old and to prolong life. The concentration of the mind is beneficial to biochemical profile of the brain and nervous system, and the flow of the internal self healing energy is beneficial to the delivery of oxygen and nutrition to the tissues. Studies found that practicing Taiji Quan is a great help to the elders. This is an indication of its immense value to men’s health, as has been testified by practice and research. In its purest form, Taiji Quan is a beautiful combination of eloquent, fluid and balanced body movement, yet it can be quite physical and is often used for defense. Because the level of input and complexity is either under the control of or susceptible to the willingness of each individual, Taiji Quan can be enjoy by all ages. This is perhaps why more and more people take to Taiji Quan. Now in China, million of citizens practice Taiji Quan every day.
Over the past three centuries, Taiji Quan has received more and more attention, and its popularity has increased, not only in China, but also gone far beyond its borders to Southeast Asia, Japan, America, European countries and many other countries.
Depression in the Workplace: Treatment Program Can Improve Productivity Outcomes
An outreach treatment program for depression in the workplace can significantly lower depressive symptoms among employees, improve job retention, reduce absences, and increase work productivity, according to Philip S. Wang, MD, and colleagues. The researchers, who reported their findings in the September 26 JAMA, believe that employers would experience a positive return on investment from such a program.
Study participants were employees of 16 large companies who screened positive for possible depression on a health risk appraisal survey and were contacted via telephone and given a survey that included the Quick Inventory of Depressive Symptomatology–Self-Report (QIDS-SR); those with a score of 8 or higher had moderate or severe depression and were eligible for randomization. A total of 304 participants were randomized to receive a free-of-charge, structured telephone intervention program that systematically assessed the need for treatment and encouraged employees to enter outpatient treatment with psychotherapy and/or antidepressant medication. The program also provided support for treatment adherence, monitored treatment quality and continuity, and made recommendations to clinicians.
Another 300 participants were randomized to usual care, informed that they had possible depression, and advised to consult with a clinician. They were allowed to access any usual available insurance benefit or service, such as psychotherapy or pharmacotherapy.
ENHANCED INTERVENTION FOR DEPRESSION
“Workers in the intervention group worked an average of two more hours per week than workers in the usual care group, which is equivalent to an annualized effect of more than two weeks of work,” noted Dr. Wang, Director of the Division of Services and Intervention Research at the NIMH, and colleagues. This, coupled with increased job retention (at 12 months, 92.6% in the intervention group vs 88% in the usual care group; odds ratio [OR], 1.7), resulted in a significant 2.6-hour improvement per week in overall work function among intervention participants. At six months, QIDS-SR scores were significantly lower among those provided with the intervention than in those who received usual care, with mean scores of 10.2 and 11.2, respectively. Substantial depression symptom improvement (≥50% reduction in QIDS-SR score) occurred in a larger proportion of the intervention group than in the usual care group at six months; by 12 months, the difference was significant (30.9% of the intervention group and 21.6% of the usual care group). More than one-quarter of the intervention group experienced recovery at 12 months with a QIDS-SR score of 5 or less, significantly greater than those receiving usual care (17.7%).
Those assigned to the intervention group were also 1.6 times more likely to receive any mental health specialty treatment compared with those in usual care, but they were less likely to receive depression treatment in primary care or nonmedical settings (ORs, 0.7 and 0.6, respectively). Intervention patients also had more treatment contacts during the 12-month study, with a mean of 12.7, compared with a mean of 6.5 treatment contacts in the usual care group.
REDUCED DEPRESSION LEADS TO EMPLOYER COST SAVINGS
Although a formal evaluation of the intervention’s return on investment to employers is not yet possible, the investigators asserted that “the $1800 annualized value of higher mean hours worked among intervention participants retaining their jobs by itself far exceeds the $100 to $400 outreach and care management costs associated with low- to moderate-intensity interventions.” They proposed that companies view outreach and enhanced care for depressed employees as an investment in worker productivity rather than a workplace cost.
In an accompanying editorial, Kenneth B. Wells, MD, and Jeanne Miranda, PhD, of the Department of Psychiatry and Biobehavioral Services at the University of California, Los Angeles, noted that depression interventions offer advantages for employees with depression, their family and friends, their employers, and society. Drs. Wells and Miranda also pointed out that insurance policy changes need to avoid undermining the goals of such programs, for example, the exclusion of depression treatment from health care coverage when an employee changes jobs or insurance, based on a recent history of treatment in an employer-based depression program. “Under such an ill-advised policy, the risk of losing coverage would serve as a major deterrent to seeking care,” they asserted.
“Learning how to optimize personal and societal gains by improving access to quality depression care across diverse communities through employer, practice, and community-based programs and policy changes is a next agenda for evidence-based action,” concluded the editorialists.
Exploring the Relationship Between Sleep, Dreams, and Memory
MINNEAPOLIS—Sleep benefits the most difficult learning tasks and helps extract the most important information from the brain, according to Robert Stickgold, PhD, who presented his view on the role that sleep plays in processing memories at the 21st Annual Meeting of the Associated Professional Sleep Societies.
“There are many, many different systems within the brain that are used for the storage and processing of information,” said Dr. Stickgold, Associate Professor of Psychiatry at Harvard Medical School in Boston. “Sleep acts to consolidate and strengthen specific memories by creating new ways of identification and creation of associations among them,” including specific details. This requires physiologic processing using a variety of distinct brain states, which may correspond with stages of sleep. “A strong hypothesis would be that varied stages of sleep originally evolved to meet the varying demands of the memory system and enhance understanding,” he added.
Within the past decade, an explosive growth in knowledge of the relationship between sleep and memory has occurred. Research conducted by Dr. Stickgold and colleagues has focused on slow-wave sleep, which precedes and follows REM sleep and is believed to be critical for memory consolidation. Slow-wave sleep has four distinct stages, from drowsiness to progressively deeper sleep. These different stages are believed to be associated with procedural learning tasks, such as learning how to play checkers or whether to take an umbrella if it looks likely to rain.
To test the theory that sleep is involved in consolidating procedural memory, Dr. Stickgold and Matthew P. Walker, PhD, a former colleague at Harvard who is now the Principal Investigator of the Sleep and Neuroimaging Laboratory in the Department of Psychology at the University of California, Berkeley, conducted experiments in which participants were trained to tap nine-digit sequences—the second-to-last digit of which was always the same—and then allowed to sleep. After a night of sleep, the volunteers were two-and-a-half times more likely to recognize the sequence pattern.
“What’s getting better on this test is a complicated question,” Dr. Stickgold said. “While we sleep, the brain sifts through and integrates all that information,” extracting information not available before we go to sleep. “[Participants] get better, but they get better differently,” he added, noting that those who recognized the sequence did not necessarily complete the sequence any faster. “It’s as if the brain has decided to focus on the details … how to take that sequence and step back and nail down exactly what I’ve learned to try to look for—a pattern or a shortcut or a meta-description. You don’t get faster, but you figure out the shortcut. It’s not time that’s important for this improvement in performance; it’s sleep itself.”
Recent data suggest that people who discovered this insight had less slow-wave REM sleep than those who did not. Some research suggests that sleep works to extract rules from specific information. “The rules don’t have to be correct,” he said; rather, the brain finds a pattern, “and this is the best it can do at trying to figure out what [that pattern] means.”
According to another study conducted with thematic word lists, “it turns out that when you see a list of words, your brain does two things,” said Dr. Stickgold. “It tries to create a memory of each and every one of those words that it saw, and it tries to create a memory of the gist of what that list was about. It has both of those memories, and it gets them confused,” in that the brain “remembers the gist long after any of the words on the list.”
One subcategory of procedural learning is perceptual memory, or how one learns to carry out various perceptual tasks. “It could be visual; it could be auditory; it could be kinesthetic; it can be the ability to reach into your pocket and [make the distinction necessary to] pull out a nickel instead of a quarter, unlike when you’re in [in a foreign country] and you have take the whole handful out,” said Dr. Stickgold. “This is a skill that’s developed slowly, mostly unconsciously, and it is consolidated across a night’s sleep.”
Dr. Stickgold noted that one unexpected source of evidence for sleep-dependent memory consolidation comes from the study of dreaming. “Dream reports, in common with microarray analyses of gene expression, single-cell and neural network recordings, and human brain images, can provide a window into the activity of the sleeping brain, albeit a subjective one,” he wrote in Nature in 2005.
Two studies suggest that episodic memories are not reactivated during dreaming, as sleep more likely protects and consolidates episodic memories, in addition to discriminating among them. In one study, volunteers who played the computer game Tetris before going to sleep reported that as they drifted off to sleep, they saw specific shapes from the game floating downward. When a group of patients with mild amnesia and bilateral damage to the hippocampus and medial temporal lobes who could no longer form new memories—to the extent that they had no memory of playing the game despite having done so for hours—were asked about their dreams, three of five reported seeing images “turned on their sides” or as “shapes on a screen,” although they could not remember what they were.
“So although those people cannot form a declarative memory that they can [recall], they still form traces of this memory in nonhippocampal regions of their brain, which holds the information in a way that they don’t have conscious access to it,” said Dr. Stickgold. “This is the path to the unconscious. They are displaying memories that, due to brain lesions, they are unable to recall during the day,” suggesting that it is not the act of playing the game that creates the Tetris images, or procedural learning, but some other feature.
In another study, 14 of 16 volunteers who played an “Alpine racer” computer game before going to sleep “reported images of skiing across three nights of sleep-onset dreaming,” Dr. Stickgold said. “Like Tetris, it has a profound impact on sleep-onset dreams,” with 42% of participants noting a skiing image the first night.
“So what happens to those images?” Dr. Stickgold asked. “Well, most of them disappear, but something even more interesting happens. We start getting reports like this: ‘I felt as if I was falling downhill.’ The brain, now having had two hours of sleep to process this information, is no longer playing it the way it happened; it’s asking different questions now: What’s that like? What other information do I have that might be relevant to this? What should link this up with? What association should I connect to this?”
He noted that one person reported, “‘I was moving forward very stiffly, my entire upper body incredibly straight; I felt like I was moving forward on a conveyor belt.’ So whatever it is that made those dreams, those images, so intrusive into our sleep-onset dreams, that’s been altered across the first two hours of sleep, so that it no longer had that intrusive quality. This is really important clinically, because that’s what fails in [patients with] PTSD [posttraumatic stress disorder]. We’ve all had those sleep-onset dreams after September 11. What should happen over time is that those memories get processed; they get integrated into our sense of self and to our understanding of the world and the trauma disappears. In those individuals for whom this doesn’t happen, the replay … continues. I would argue that this is a failure of sleep-dependent memory processing…. It’s as if the brain is trying to create meaning, and the way we create meaning is by taking information and embedding it in our general knowledge. After September 11, people said, ‘I don’t understand what happened.’ It’s not that they didn’t understand [a plane] crashing into a building. They understood that; they didn’t understand what that meant about their life. They didn’t know if they should go to work [the next day]. They didn’t know if they should take public transportation. They didn’t know if they should get on that plane with ‘that guy who looks a little different to me.’ It’s that kind of understanding that is probably the most sophisticated conditioning the brain does.”
Physical Aspects of the Brain
The brain is safely secured in your head. It should not be confused with the mind. The brain is physical; the mind is functional. The brain is the hardware, the mind is the software.
There are approximately 100 billion neurons in the brain. The adult brain weighs about 1.4 kg and is only 2 percent of the body weight.
The brain has three major parts; the brain stem, cerebellum, and cerebrum.
The brain stem sits atop your spinal column. This is the first part of the brain to be formed in the womb. It has three nerve centres- the midbrain, pons and medulla oblongata. The nerve centres in the midbrain help control movements of the eye. The pons links the two hemispheres of the crebrum. The medulla regulates breathing, heartbeat and blood flow. In short, the brain stem takes care of the survival mechanism of the body.
The cerebellum is ocated just behind the brain stem and manages the movement of our body. Therefore, it contains memory for movement. Thei is called kinaesthetic memory or muscle memory. Most good athletes have very well developed cerebellums.
The crebrum is the final stage of brain development in evolution. this the real brain where thinking and feelings arise. The cerebrum is divided into four areas or lobes:
-> the frontal lobe deals with abstract problem solving.
->the parietal lobe helps process information from the sense.
-> the occipital lobe governs vision and
->the temporal lobe controls memory, hearing and language.
the cerebrum contains the neocortex and limbic system. these two work in tandem. The neocortex is the thinking brain and limbic system is the feeling brain. the limbic system is where the mind meets the body and the endocrine system interfaces with the brain. It is also where thought meets emotions. when the physical health of the limbic system is stimulated, one can effectively operate the intellectual and emotional aspects of life.
The primary parts of the limbic system ate the
the brain generates electricity. the brain cells run on electricity and the brain has enough electricity to light a 25 watt bulb. thoughts travel through brain cells on electrical currents. Long strings of brain cells light up with electrical energy to form complete and emotions.
Most brain cells are elongated, shaped rather like trees with a branch system. The roots of the neuron are called axons. Information flows into axons form the dentric branches of adjacent neurons. Information travels to the axons of another neuron in the form of an electrical impulse. Eventually, this forms a complete chain like thought or memory. New dentric branches can be stimulated to grow.
EXPLORING THE BRAIN’S ROLE IN CREATIVITY
EXPLORING THE BRAIN’S ROLE IN CREATIVITY
SAN DIEGO—Being one of the true geniuses of the modern era, Albert Einstein recognized that a useful method for understanding the brain’s role in creativity was to study the brains of highly creative people. He also realized that there would be a great deal of interest in examining his own brain after his death, so he willed that his brain be removed before cremation. However, nearly all of the 240 blocks into which Einstein’s brain was dissected were lost and never analyzed.
Thirty years later, the Brodmann’s area 39 portion of Einstein’s brain was analyzed histologically by Marian C. Diamond, PhD, and colleagues. They reported that this area of Einstein’s brain contained a higher proportion of glial cells versus neurons, compared with the brains of control subjects. Assuming that the paucity of cortical neurons was not the result of aging (the control subjects were significantly younger than Einstein at the time of his death), how did the loss of neurons relate to Einstein’s creative genius?
When Einstein was about age 3, his parents brought him to a pediatrician because he was not yet talking. Researchers have learned that Einstein had developmental dyslexia. More than a century ago, it was found that lesions of the left angular gyrus—ie, Brodmann’s area 39—induce acquired alexia. Therefore, it is possible that people with developmental dyslexia may also have abnormalities in this region, Kenneth M. Heilman, MD, suggested in his lecture at the 17th Annual Meeting of the American Neuropsychiatric Association. In his view, however, the high ratio of glial cells to neurons that was reported by Diamond et al was less a sign of Einstein’s dyslexia than an indication of the high degree of what Dr. Heilman refers to as "connectivity."
After viewing photographs taken of Einstein’s brain before its dissection in 1955, Witelson and colleagues noted that Einstein had an enlarged left inferior and—unlike most human beings—undivided parietal lobe, suggesting that this bigger and more highly connected supramodal cortex gave Einstein an advantage in doing mathematics and spatial computations. In 1985, Geschwind and Galaburda posited that delay in the development of the left hemisphere of the brain may allow the right hemisphere, which mediates spatial computations, to become highly specialized. It was Einstein’s view that his own creativity was heavily dependent on spatial reasoning. Thus, the abnormal development of his left hemisphere may have led to the right hemisphere becoming highly specialized for spatial computations, Dr. Heilman theorized.
"If you have something going on in one side of the brain, [could] that ‘disinhibit’ the other side of the brain [into] developing even greater ability?" Dr. Heilman asked. "Could Einstein’s dyslexia and lack of development of his left hemisphere have allowed his right hemisphere to grow and be well connected and to have excellent modules?... People who have tremendous creativity also have tremendous connectivity."
FINDING THE THREAD THAT UNITES
According to Dr. Heilman, who is the James E. Rooks, Jr, Distinguished Professor of Neurology and Health Psychology at the University of Florida’s College of Medicine in Gainesville, connectivity is a key component of "creative innovation," a concept that combines two of the four stages of creativity—incubation and illumination (the others are preparation and verification)—identified by Hermann Helmholtz in 1826.
In an article titled "Creative Innovation: Possible Brain Mechanisms" appearing in Neurocase in 2003, Dr. Heilman and his colleagues, Stephen E. Nadeau, MD, and David O. Beversdorf, MD, defined creative innovation as "the ability to understand and express novel orderly relationships." A high level of general intelligence, domain-specific knowledge, and special skills are necessary for creative innovation, but even when they coincide, these three components are not sufficient for creative innovation. One further crucial component is the ability to develop alternative solutions—otherwise known as "divergent thinking"—yet, even the coexistence of specialized knowledge and divergent thinking is not enough to enable an individual to find the thread that unites the two.
"Finding this thread might require the binding of different forms of knowledge, stored in separate cortical modules that have not been previously associated," the authors wrote. "Thus, creative innovation might require the coactivation and communication between regions of the brain that ordinarily are not strongly connected."
Based on the findings of anatomic studies, it appears that creative individuals such as Einstein may have alterations of specific regions of the brain’s posterior neocortical region. At the same time, it has been observed that creative innovation frequently takes place during times of diminished arousal (eg, sleep) and that many well-known creative people have experienced depression, suggesting that alterations of such neurotransmitters as norepinephrine might play a critical role in creativity. In the view of Dr. Heilman and his coauthors, highly creative individuals "may be endowed with brains that are capable of storing extensive specialized knowledge in their temporoparietal cortex, be capable of frontal mediated divergent thinking, and have a special ability to modulate the frontal lobe-locus coeruleus (norepinephrine) system, such that during creative innovation cerebral levels of norepinephrine diminish, leading to the discovery of novel orderly relationships."
In his lecture and in a follow-up interview with NeuroPsychiatry Reviews, Dr. Heilman focused on the importance of divergent thinking in creative innovation, how our understanding of its neurobiologic underpinnings has evolved over the past two centuries, and the clinical implications of depression and other brain disorders for future neuropharmacologic treatments.
"To be creative, people need to break away from what they have been taught to believe, and thus divergent thinking is a critical element of creativity," he said. "Patients who have their frontal lobe[s] removed or injured cannot perform divergent thinking…. The major hypothesis of this talk is that creativity is dependent upon the ability to diverge and then form innovative solutions.
"The development of innovative solutions is dependent on the ability to coactivate anatomically distinct representational networks that store different forms of knowledge. This simultaneous distributed activation … may allow people to develop alternative innovative solutions, thereby finding the thread that unites."
ENCOURAGING CREATIVITY BY FOSTERING INDEPENDENT THINKING
Dr. Heilman cited several items that are important for clinicians to know to get a handle on current research into creativity and the brain. Besides the importance of both divergent and "convergent" thinking, he observed that "many people who are very creative have a higher incidence of mood and addiction disorders [and that while] many neurologic disorders can reduce creativity … there are some that might enhance creativity."
As an example of the latter, he cited the work of Miller and colleagues at the University of California, San Francisco, describing a series of patients with frontotemporal dementia who acquired new artistic abilities despite evidence of deterioration in the left anterior temporal lobe (see NeuroPsychiatry Reviews, June 2003, page 1). "These are people who had no history of artistic production," Dr. Heilman said. "They actually became creative—perhaps because the deterioration on the left side ‘disinhibited’ their right side, and the right side got creative doing artistic things."
Regarding mood and addiction disorders, Dr. Heilman explored the links among creativity and sleep, dreaming, rest and relaxation, and depression, and observed that one thread uniting them all is changes in neurotransmitter systems. Two components indispensable to divergent thinking appear to be disengagement and the ability to develop alternative solutions. To arrive at a creative solution to a persistently unsolvable problem, an individual must often change the method by which he or she has already attempted to solve the problem—in other words, think outside the box. Observations on problem solving have included William James’ view, expressed in 1890, that the ability to switch strategies is integral to divergent thinking and Charles Spearman’s suggestion in 1931 that creativity results from bringing together two or more ideas that previously have been isolated. One way to solve a persistent problem, then, would be to see it in a "new light" by combining different forms of knowledge and cognitive strategies mediated by the two hemispheres of the brain.
Dr. Heilman cited as examples a number of scientists who reported solving a difficult scientific problem while asleep or when falling asleep or awakening from sleep. He also pointed to the association between creativity and novelty seeking and the high rates of alcoholism, drug abuse, bipolar depression, and monodepression among such creative types as writers, composers, musicians, and fine artists. Based on what is known from existing evidence, such associations raise more questions than answers, according to Dr. Heilman. "For example, does treatment of depression and bipolar disorder influence creativity, and what are the effects of different treatments?" he asked.
PROMOTING CREATIVE THINKING
Can creativity in individuals be encouraged regardless of the makeup of their brain, or are we limited by such factors as the number of glial cells and amount of white matter? "I believe creativity can be ‘encouraged,’" Dr. Heilman responded. "We have known for decades that when young rodents are put in a stimulating environment, they have a much richer neural network than their sibs who were not raised in this environment. Thus, bringing up children in an enriched environment and making certain that they receive a good education is critical for their brain development.
"The frontal lobes appear to be the part of the cortex that is most important for creativity, in that they are critical for divergent thinking and might modulate the coactivation of diverse cognitive networks so important in innovation. The means by which family and friends might be able to encourage the development of the frontal lobes is to encourage independent and divergent thinking."
Apart from such sociocultural interventions, Dr. Heilman believes that there is a limit to the extent to which neuropsychiatry and neuroscience can enhance creativity, particularly with regard to the development of new neuropharmacologic treatments. "It is possible that certain drugs taken by people might enhance creativity and others inhibit creativity," he said, citing an editorial titled "Cosmetic Neurology," written by one of his former fellows, Anjan Chatterjee. "But physicians have learned that ‘when it is not broke, do not attempt to fix it.’ In other words, if you alter a person’s homeostasis, there might be a price paid."
Creativity
left brain vs Right Brain Thinking
brain
LWW Budget Brain
with Arteries
The human brain is physically divided into two connected hemispheres, left and right. Research has shown that although these two halves of the brain work closely together there is a definite degree of specialisation, a process kown as lateralisation (or "lateralizaion"). The degree to which this takes place is open to dispute. It certainly exists at some level but probably not to the extent claimed by some pop psychology. Regardless of that it still provides an interesting and useful metaphor for considering creativity.
Cerebral Specialisation
In general the left side of the brain is usually associated with logical, reasoning type activity. It plays safe and follows systematic, convergent patterns of thought. Mathematics and language are often associated with the left brain.
The right side of the brain is usually associated with visual and musical activitty, emotional empathy, etc. It takes risks and makes leaps of divergent thought. It is often known as the artistic side of the brain.
For example: When you saw the word "Brains" in the section index, did you think of neurology? Or of zombies?
Someone - I forget who - once told me an excellent mnemonic for remembering which side is which:
L is Logical
R is Artistic
Lateralisation and Creativity
Both sides of the brain are needed for the complete creative process. However the right side is the one most needed for the initial, idea generating phase. It is the right side of the brain that is more useful in generating new ideas and synthesising concepts, in breaking away from conventional patterns of thought. The left side of the brain is better at analysing and criticising these new ideas. Very often "left brain" functionality is applied too early in the creative process and ideas are rejected as "impractical" before being fully explored.
Unfortunately our society tends to value "left brain thinking" more than right. In particular much of our education system stresses left brain activity.
Many creativity techniques and courses stress ways to enhance and stimulate right brain activity. Once the right brain has generated creative ideas then the left brain can be usefully called upon to sort, sift and analyse them in detail.A new study attempts to answer the question of whether people who are creative problem solvers have different brain activity patterns than the less creative.
A new study led by John Kounios, professor of Psychology at Drexel University and Mark Jung-Beeman of Northwestern University answers these questions by comparing the brain activity of creative and noncreative problem solvers. The study, a published “Article in Press” in the journal Neuropsychologia, reveals a distinct pattern of brain activity, even at rest, in people who tend to solve problems with a sudden creative insight -- an “Aha! Moment” – compared to people who tend to solve problems more methodically.
At the beginning of the study, participants relaxed quietly for seven minutes while their electroencephalograms (EEGs) were recorded to show their brain activity. The participants were not given any task to perform and were told they could think about whatever they wanted to think about. Later, they were asked to solve a series of anagrams – scrambled letters that can be rearranged to form words [MPXAELE = EXAMPLE]. These can be solved by deliberately and methodically trying out different letter combinations, or they can be solved with a sudden insight or “Aha!” in which the solution pops into awareness. After each successful solution, participants indicated in which way the solution had come to them.
The creative types had patterns of resting brain activity that were different from the patterns of brain activity seen in non-creative types.
The participants were then divided into two groups – those who reported solving the problems mostly by sudden insight, and those who reported solving the problems more methodically – and resting-state brain activity for these groups was compared. As predicted, the two groups displayed strikingly different patterns of brain activity during the resting period at the beginning of the experiment – before they knew that they would have to solve problems or even knew what the study was about.
One difference was that the creative solvers exhibited greater activity in several regions of the right hemisphere. Previous research has suggested that the right hemisphere of the brain plays a special role in solving problems with creative insight, likely due to right-hemisphere involvement in the processing of loose or “remote” associations between the elements of a problem, which is understood to be an important component of creative thought. The current study shows that greater right-hemisphere activity occurs even during a “resting” state in those with a tendency to solve problems by creative insight. This finding suggests that even the spontaneous thought of creative individuals, such as in their daydreams, contains more remote associations.
What I want to know: does the creative style of thinking have a genetic cause? If it does then when people start genetically engineering their offspring will they choose the genetic variations that cause creativity more often or less often than it now occurs naturally? In other words, will genetic engineering boost the amount of creative thinking in the world?
Second, creative and methodical solvers exhibited different activity in areas of the brain that process visual information. The pattern of “alpha” and “beta” brainwaves in creative solvers was consistent with diffuse rather than focused visual attention. This may allow creative individuals to broadly sample the environment for experiences that can trigger remote associations to produce an Aha! Moment.
This pattern of diffuse attention reminds me of low latent inhibition. See my post Low Latent Inhibition Plus High Intelligence Leads To High Creativity?
Children Of Bipolar Parents More Creative
Creative and mentally ill parents have creative and mentally ill children.
STANFORD, Calif. – Researchers at the Stanford University School of Medicine have shown for the first time that a sample of children who either have or are at high risk for bipolar disorder score higher on a creativity index than healthy children. The findings add to existing evidence that a link exists between mood disorders and creativity.
The small study, published in the November issue of the Journal of Psychiatric Research, compared creativity test scores of children of healthy parents with the scores of children of bipolar parents. Children with the bipolar parents—even those who were not bipolar themselves—scored higher than the healthy children.
Obviously genetics plays an important role in creativity, ADHD, and bipolar disorder.
Artists have higher rates of mental illness.
Many scientists believe that a relationship exists between creativity and bipolar disorder, which was formerly called manic-depressive illness and is marked by dramatic shifts in a person’s mood, energy and ability to function. Numerous studies have examined this link; several have shown that artists and writers may have two to three times more incidences of psychosis, mood disorders or suicide when compared with people in less creative professions.
Terence Ketter, MD, professor of psychiatry and behavioral sciences and a study co-author, said he became interested in the link between mental illness and creativity after noticing that patients who came through the bipolar clinic, despite having problems, were extraordinarily bright, motivated people who “tended to lead interesting lives.” He began a scholarly pursuit of this link and in 2002 published a study that showed healthy artists were more similar in personality to individuals with bipolar disorder (the majority of whom were on medication) than to healthy people in the general population.
Some people with higher intellectual capabilities might be able to handle their bipolar and ADHD and still manage to be productive. But less bright people are probably more likely to be overwhelmed by their mental illness and unable to harness their creativity for productive purposes. But do the genetic variations that contribute to causing bipolar also raise IQ?
People who use their negative emotions to initiate searches for solutions to problems tend to be more creative.
The children of parents with bipolar disorder were themselves either bipolar or had ADHD (attention deficit hyperactivity disorder).
During the study, the researchers looked at creative characteristics in 40 bipolar patients and 40 offspring, comparing them with 18 healthy adults and 18 healthy offspring. The children in the study ranged in age from 10 to 18. Half of the children of bipolar patients also had bipolar disorder; the other half had attention deficit hyperactivity disorder or ADHD, which appears to be an early sign of bipolar disorder in offspring of parents with the condition. The majority of participants with bipolar or ADHD were on medication.
The researchers included children with ADHD so they could study creativity before the onset of full bipolar disorder. “We wanted to see whether having a manic episode is necessary for this sort of creativity,” said Chang, who also directs the Pediatric Bipolar Disorders Program at Lucile Packard Children’s Hospital.
Study participants were given psychiatric evaluations and then completed the Barron-Welsh Art Scale, or BWAS, a test that seeks to provide an objective measure of creativity. The scoring is based on “like” and “dislike” responses to figures of varying complexity and symmetry; past studies suggest that creative people tend to dislike the simple and symmetric symbols.
The researchers found that the bipolar parents had 120 percent higher BWAS “dislike” scores than the healthy parents. The children with bipolar and the children with ADHD had, respectively, 107 and 91 percent higher BWAS dislike scores than the healthy children.
“The results of this study support an association between bipolar disease and creativity and contribute to a better understanding of possible mechanisms of transmission of creativity in families with genetic susceptibility for bipolar disease,” the researchers wrote in their paper.
On the bright side, the bipolar mania stage is not needed to cause creativity. The presence of ADHD alone boosts creativity. The problem, though, is that people with ADHD might be full of ideas. But many lack the patience needed to translate their ideas into implementations. If you can't stand to focus long enough to write down the melody or story line you see in your head or to draw a mechanical design that you've thought of your creativity doesn't do you or the world much good.
The researchers had hypothesized that the scores of children with ADHD would differ significantly from the scores of bipolar children so they were surprised when the scores did not. Chang said this indicates that mania is not what is fueling the creativity. “The kids with ADHD who hadn’t been manic yet still had very high levels of creativity,” he said.
Being mentally ill for a longer time erodes the BWAS dislike score. Mentally ill people burn out and cease to be creative.
The researchers also found a link between the length of a bipolar child’s illness and creativity: the longer a child was sick or manic, the lower the BWAS dislike score. It makes sense, Chang said, that this illness could, over time, erode one’s creativity. “After awhile you aren’t able to function and you can’t access your creativity,” he explained.
We all get less creative with age.
BWAS dislike scores tend to decrease with age even in healthy individuals, so more research is needed, Ketter said. Further studies are also needed to assess the role of genetic and environmental factors in creativity and bipolar, he added. The team plans to next examine whether the degree of creativity in parents correlates with the degree of creativity in their children.
If the mental illness eventually leads to declining creatvitiy by causeing neuronal cell death then perhaps the development of treatments based on Strategies for Engineered Negligible Senescence (SENS) will provide ways to preserve neurons and creativity as the years and decades go by.
Maybe one cause of hyperactivity is a low threshold for noticing external stimuli. See my previous post "Low Latent Inhibition Plus High Intelligence Leads To High Creativity?"
Brain Scans Show Why Schizotypal Personalities More Creative
Schizotypal personalities are more creative.
New research on individuals with schizotypal personalities – people characterized by odd behavior and language but who are not psychotic or schizophrenic – offers the first neurological evidence that they are more creative than either normal or fully schizophrenic individuals, and rely more heavily on the right sides of their brains than the general population to access their creativity.
The work by Vanderbilt psychologists Brad Folley and Sohee Park was published online last week by the journal Schizophrenia Research.
"The idea that schizotypes have enhanced creativity has been out there for a long time but no one has investigated the behavioral manifestations and their neural correlates experimentally," Folley says. "Our paper is unique because we investigated the creative process experimentally and we also looked at the blood flow in the brain while research subjects were undergoing creative tasks."
Folley and Park conducted two experiments to compare the creative thinking processes of schizotypes, schizophrenics and normal control subjects. In the first experiment, the researchers showed research subjects a variety of household objects and asked them to make up new functions for them. The results showed that the schizotypes were better able to creatively suggest new uses for the objects, while the schizophrenics and average subjects performed similarly to one another.
"Thought processes for individuals with schizophrenia are often very disorganized, almost to the point where they can’t really be creative because they cannot get all of their thoughts coherent enough to do that," Folley observes. "Schizotypes, on the other hand, are free from the severe, debilitating symptoms surrounding schizophrenia and also have an enhanced creative ability."
So then is creativity just the result of unusual brain anatomy?
Brain scans showed that schizotypes use more of their right hemispheres for creative work than do normal or schizophrenic people.
In the second experiment, the three groups again were asked to identify new uses for everyday objects as well as to perform a basic control task while the activity in their prefrontal lobes was monitored using a brain scanning techniques called near-infrared optical spectroscopy. The brain scans showed that all groups used both brain hemispheres for creative tasks, but that the activation of the right hemispheres of the schizotypes was dramatically greater than that of the schizophrenic and average subjects, suggesting a positive benefit of schizotypy.
"In the scientific community, the popular idea that creativity exists in the right side of the brain is thought to be ridiculous, because you need both hemispheres of your brain to make novel associations and to perform other creative tasks," Folley says. "We found that all three groups, schizotypes, schizophrenics and normal controls, did use both hemispheres when performing creative tasks. But the brain scans of the schizotypes showed a hugely increased activation of the right hemisphere compared to the schizophrenics and the normal controls."
Suppose the schizotypes have some genetic component to how their brains work. Once genetic engineering of offspring becomes possible or even once detailed genetic testing of fertilized eggs becomes possible will future parents make choices that decrease the fraction of the population that have brain wiring that make them especially creative?
Or, more optimistically, will genetic variations be found that increase creativity while lowering risk of mental disorders?
Functional MRI (fMRI) brain scans show the location of activity in the brain of visual short-term working memory.
The amount of information we can remember from a visual scene is extremely limited and the source of that limit may lie in the posterior parietal cortex, a region of the brain involved in visual short-term memory, Vanderbilt psychologist René Marois and graduate student J. Jay Todd have found. Their results were published in the April 15 edition of Nature.
Previous findings have determined that an extensive network of brain regions supports visual short-term memory. In their study, Todd and Marois showed that the severely limited storage capacity of visual short-term memory is primarily associated with just one of these regions, the posterior parietal cortex.
Todd and Marois used functional magnetic resonance imaging (fMRI), a technique that reveals the brain regions active in a given mental task by registering changes in blood flow and oxygenation in these regions, to identify where the capacity limit of visual short-term memory occurs.
The brains of research participants were scanned with fMRI while they were shown scenes containing one to eight colored objects. After a delay of just over a second, the subjects were queried about the scene they had just viewed.
While the subjects were good at remembering all of the objects in scenes containing four or fewer objects, they frequently made mistakes describing displays containing a larger number of objects, indicating that the storage capacity of visual short-term memory is about four.
The fMRI results revealed that activity in the posterior parietal cortex strongly correlated with the number of objects the subjects were able to remember. The magnitude of the neural response in this brain area increased with the number of objects viewed up to about four and leveled off after that, even when additional objects were presented.
A different team led by Edward Vogel of the University of Oregon at Eugene were able to use signals measured by electrodes attached to the scalp to precisely measure the size of each person's visual working memory.
A large increase in the subject's brain activity on the four-dot test indicated that his or her memory capacity had not been pushed to its limit. No increase in electrical activity indicated that his or her working memory had topped out on the two-dot test. By graphing these responses, the team worked out the exact size of each subject's working memory.
It is likely that the measured differences in visual memory have some genetic basis. With that in mind it would be interesting to use Vogel's technique to compare measured visual working memory with BDNF gene variations that affect visual and episodic memory capabilities.
Another team at Northwestern University and Drexel University has used fMRI to demonstrate that the problem solving mechanism that produces the "Eureka!" moment of discovering an answer works by a different mental mechanism than what is used to solve problems by more conventional methods.
While several regions in the cerebral cortex showed about the same heightened activity for both insight and noninsight-derived solutions, only an area known as the anterior Superior Temporal Gyrus (aSTG) in the right hemisphere (RH) showed a robust insight effect. The researchers also found that 0.3 seconds before the subjects indicated solutions achieved through insight, there was a burst of neural activity of one particular type: high-frequency (gamma band) activity that is often thought to reflect complex cognitive processing. This activity was also mapped to the aSTG of the RH, providing compelling convergence across experiments and methods.
Problem-solving involves a complex network of brain regions to encode, retrieve, and evaluate information, but these results show that solving verbal problems with insight requires at least one additional component. Further, the fact that the effect occurred in RH aSTG suggests what that process may be: integration of distantly related information. Distinct neural processes, the authors conclude, underlie the sudden flash of insight that allows people to "see connections that previously eluded them."
Some problems are easier to solve because they require the use of straightforward procedures which has been trained to use. For example, if one solves a math problem with a known method of solution then there is no "Eureka!" moment when one calculates the answer. Whereas when a solution found by noticing previously unobserved connections there is more a sense of revelation. It is this latter case that involves a burst of activity in a part of the brain called the anterior Superior Temporal Gyrus (aSTG).
Mark Jung-Beeman says these results demonstrate that "Eureka!" moments are different than moments when problems are solved with conventional methods.
“For thousands of years, people have said that insight feels different from more straightforward problem-solving,” he said.
“We believe this is the first research showing that distinct computational and neural mechanisms lead to these breakthrough moments.”
The paper by Mark Jung-Beeman et. al. is available online here: Neural Activity When People Solve Verbal Problems with Insight.
It would be interesting to know whether people who are considered more creative in their fields have a bigger anterior Superior Temporal Gyrus (aSTG). Every time a part of the brain is discovered as key for some function the obvious question that arises is just how valuable would it be to enhance that part of the brain. The aSTG for reaching insights and the posterior parietal cortex for working short-term visual memory both strike me as useful areas to enhance to make one better at scientific and engineering work.
Low Latent Inhibition Plus High Intelligence Leads To High Creativity?
Jordan Peterson of the University of Toronto and colleages at Harvard University have found that decreased latent inhibition of environmental stimuli appears to correlate with greater creativity among people with high IQ. (same press release available here and here)
The study in the September issue of the Journal of Personality and Social Psychology says the brains of creative people appear to be more open to incoming stimuli from the surrounding environment. Other people's brains might shut out this same information through a process called "latent inhibition" - defined as an animal's unconscious capacity to ignore stimuli that experience has shown are irrelevant to its needs. Through psychological testing, the researchers showed that creative individuals are much more likely to have low levels of latent inhibition.
"This means that creative individuals remain in contact with the extra information constantly streaming in from the environment," says co-author and U of T psychology professor Jordan Peterson. "The normal person classifies an object, and then forgets about it, even though that object is much more complex and interesting than he or she thinks. The creative person, by contrast, is always open to new possibilities."
Previously, scientists have associated failure to screen out stimuli with psychosis. However, Peterson and his co-researchers - lead author and psychology lecturer Shelley Carson of Harvard University's Faculty of Arts and Sciences and Harvard PhD candidate Daniel Higgins - hypothesized that it might also contribute to original thinking, especially when combined with high IQ. They administered tests of latent inhibition to Harvard undergraduates. Those classified as eminent creative achievers - participants under age 21 who reported unusually high scores in a single area of creative achievement - were seven times more likely to have low latent inhibition scores.
The authors hypothesize that latent inhibition may be positive when combined with high intelligence and good working memory - the capacity to think about many things at once - but negative otherwise. Peterson states: "If you are open to new information, new ideas, you better be able to intelligently and carefully edit and choose. If you have 50 ideas, only two or three are likely to be good. You have to be able to discriminate or you'll get swamped."
"Scientists have wondered for a long time why madness and creativity seem linked," says Carson. "It appears likely that low levels of latent inhibition and exceptional flexibility in thought might predispose to mental illness under some conditions and to creative accomplishment under others."
A less able mind has a greater need to be able to filter out and ignore stimuli. A less intelligent person with a low level of latent inhibition for filtering out familiar stimuli may well sink into mental illness as a result. But a smarter mind can handle the effects of taking note of a larger number of stimuli and even find interesting and useful patterns by continually processing a larger quantity of familiar information.
You can find the original paper here: Decreased Latent Inhibition Is Associated With Increased Creative Achievement in High-Functioning Individuals (PDF format)
The central idea underlying our research program is therefore that individuals characterized by increased plasticity (extraversion and openness)retain higher post-exposure access to the range of complex possibilities laying dormant in so-called ‘‘familiar ’’environments.This heightened access is the subjective concomitant of decreased latent inhibition,which allows the plastic person increased incentive-reward-tagged appreciation for hidden or latent information
Note from the text of the full paper that stress causes the release of the hormone corticosterone which lowers latent inhibition. In a nutshell, when an organism runs into problems that cause stress the resulting release of stress hormones causes the mind to shift into a state where it will examine factors in the environment that it normally ignores. This allows the organism to look for solutions to the stress-causing problem that would be ignored in normal and less stressed circumstances.
So perhaps we could hypothesize something like this:under stressful conditions,or in person-ality configurations characterized by increased novelty-sensitivity,approach behavior,and DA activity, decreased LI is associated with increased permeability and flexibility of functional cog- nitive and perceptual category [see Barsalou (1983)for a discussion of such categories ].Imagine a situation where current plans are not producing desired outcomes —a situation where current categories of perception and cognition are in error, from the pragmatic perspective. Something anomalous or novel emerges as a consequence (Peterson,1999), and drives exploratory behavior. Stress or trait-dependent decreased LI, under such circumstances, could produce increased signal (as well as noise), with regards to the erroneous pattern of behavior and the anomaly that it produced. This might offer the organism, currently enmeshed in the consequences of mistaken presuppositions, the possibility of gathering new information, where nothing but categorical certainty once existed. Decreased LI might therefore be regarded as advantageous, in that it allows for the perception of more unlikely, radical and numerous options for reconsideration, but disadvantageous in that the stressed or approach-oriented person risks ‘‘drowning in possibility,’’ to use Kierkegaard ’s phrase.
One can easily see how this response could have been selected for evolutionarily. At the same time, one can also see how chronic stress could lead a person to fall into a state of confusion as a sustained large flood of stimuli could overwhelm the brain by giving it too much to think about and make a person unable to clearly see solutions that will relieve the feeling of stress.
THE CHEMICAL ENVIRONMENT OF THE BRAIN
INTRODUCTORY REMARKS
Most of the previous chapters of this series have emphasized gross organization and structure of the brain. This has been essential in order to gain perspective, but from a cryonicist's point of view preservation of the "the anatomical basis of mind" will ultimately mean preservation of the structures only visible under a microscope. Understanding what structures to look-for and how those structures might best be preserved is the ultimate goal of this series.
As a step in the direction towards understanding finer structure, this chapter will examine the brain from a more chemical point of view than the previous installments -- with particular reference to the gross anatomy and function of neurotransmitters in the brain.
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II. THE CHEMICAL ENVIRONMENT OF THE BRAIN
Skull surface dissection [Skull surface dissection]
The brain has the consistency of firm jelly, and therefore is protectively encased in a thick, bony skull. The brain literally floats in about 150 millilitres (mL) of CerebroSpinal Fluid (CSF) secreted by the choroid plexus. Approximately 500 mL of CSF is secreted daily, which slowly circulates down through the four ventricles, up through the subarachnoid space and exits into the cerebral veins through the arachnoid villi. The brain has no lymphatic system, so the CSF serves as a partial substitute.
Skull section [Skull section]
Brain ventricles [Brain ventricles]
The dura mater is a tough, protective connective tissue which is tightly bound to the skull, but which encases the cerebral veins. Under the dura mater is the subarachnoid space containing CSF, arteries and web-like strands of connective/supportive tissue called the arachnoid ("spider-like") mater. The pia mater is a permeable membrane of collagen, elastin fibers & fibroblasts on the floor of the subarachnoid space which allows diffusion between the CSF and the interstitial fluid of the brain tissue. The pia mater lies on a membrane that is infiltrated with astrocyte processes. The dura mater, the arachnoid mater and the pia mater are collectively referred-to as the meninges.
Skull Medial Cross-Section showing CSF flow [Skull Medial Cross-Section showing CSF flow]
Blood-Brain Barrier [Blood-Brain Barrier]
While the brain & CSF are separated by the somewhat permeable pia mater, the blood-cerebrospinal fluid barrier and the blood-brain barrier (BBB) represent substantial protection for the brain against undesirable blood substances. These barriers are very permeable to water, oxygen, carbon dioxide and small lipid-soluble substances. They are also somewhat permeable to small electrolytes -- and special transport systems exist for some other specific molecules such as essential amino acids. The barriers are the result of endothelial cells which line capillary walls -- and glial cells called astrocytes which wrap the capillaries with fibers.
The brain is not only a functionally distinct organ, it is a chemically distinct one. 50% of dry brain weight is lipid (in contrast to 6-20% for other organs). Most of the brain lipid is structural (in myelin or membranes) in contrast to the triglycerides and free fatty acids constituting the fat of other organs. The blood-brain barrier creates a protected chemical environment for the brain wherein certain molecules can perform functions independent of the functions those molecules perform in the rest of the body. This is particularly important for the neurotransmitters serotonin (which is highly concentrated in platelets & the intestine) and norepinephrine (which affects blood pressure & metabolism). All of the known amino-acid neurotransmitters are non-essential amino acids. This means that they can be manufactured in the brain, without needing to be supplied from outside the brain. But in the major area of the brain which does not have a blood-brain barrier -- the hypothalamus -- the primary neurotransmitters are peptides.
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III. GENERAL COMMENTS ABOUT NEUROTRANSMITTERS
The three major categories of substances that act as neurotransmitters are (1) amino acids (primarily glutamic acid, GABA, aspartic acid & glycine), (2) peptides (vasopressin, somatostatin, neurotensin, etc.) and (3) monoamines (norepinephrine, dopamine & serotonin) plus acetylcholine. The major "workhorse" neurotransmitters of the brain are glutamic acid (=glutamate) and GABA. The monoamines & acetylcholine perform specialized modulating functions, often confined to specific structures. The peptides perform specialized functions in the hypothalamus or act as co-factors elsewhere in the brain. [For a well-organized categorization of neurotransmitters, see Neurotransmitter (Wikipedia).]
Although there are many neurotransmitters in the central nervous system, the peripheral nervous system has only two: acetylcholine and norepinephrine. Why are there so many brain neurotransmitters? Because the functions performed by brain neurotransmitters are not as uniform as they might superficially appear. Some (like glutamate) are excitatory, whereas others (like GABA) are primarily inhibitory. In many cases (as with dopamine) it is the receptor which determines whether the transmitter is excitatory or inhibitory. Receptors can also determine whether a transmitter acts rapidly by direct action on an ion channel (eg, nicotinic acetylcholine receptors) or slowly, by a second-messenger system that allows for synaptic plasticity (eg, muscarinic acetylcholine receptors). Speed & mechanism of transmitter inactivation after the signal has been sent is also a factor. There are probably also costs & benefits involved in synthesizing, transporting and recycling various neurotranmitters in the differing chemical mileus of the brain.
Many of these issues will become more clear in discussing the synthesis, distribution and function of the major brain neurotransmitters.
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IV. GLYCINE
[General Amino Acid]
Glycine Glycine
Glycine is the simplest of amino acids, consisting of an amino group and a carboxyl (acidic) group attached to a carbon atom. Glycine's function as a neurotransmitter is also fairly simple. When released into a synapse, glycine binds to a receptor which makes the post-synaptic membrane more permeable to Cl- ion. This hyperpolarizes the membrane, making it less likely to depolarize. Thus, glycine is an inhibitory neurotransmitter. It is de-activated in the synapse by a simple process of reabsorption by active transport back into the pre-synaptic membrane.
Glycine is a neurotransmitter only in vertebrate animals. The glycine receptor is primarily found in the ventral spinal cord. Strychnine is a glycine antagonist which can bind to the glycine receptor without opening the chloride ion-channel (ie, it inhibits inhibition). The resultant spinal hyperexcitability is what makes strychnine a poison. Quoting from the ENCYCLOPEDIA BRITANNICA:
"Symptoms of poisoning usually appear within 20 minutes, starting with stiffness at the back of the neck, twitching of the muscles, and a feeling of impending suffocation. The patient is then seized with violent tetanic convulsions in which the body is arched and the head bent backward. After a minute the muscles relax, and the patient sinks back exhausted, heightened perceptiveness being perceived throughout due to sensory cortex stimulation. A touch, a noise or some other stimulus causes the convulsions to recur; or they may recur spontaneously, often at intervals of a few minutes. Strychnine poisoning is ultimately the result of suffocation or exhaustion."
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V. ASPARTIC ACID (ASPARTATE)
Aspartate Aspartate
Like glycine, apartate is primarily localized to the ventral spinal cord. Like glycine, aspartate opens an ion-channel and is inactivated by reabsorption into the pre-synaptic membrane. Unlike glycine, however, apartate is an excitatory neurotransmitter, which increases the likelihood of depolarization in the postsynaptic membrane. Aspartate & glycine form an excitatory/inhibitory pair in the ventral spinal cord comparable to the excitatory/inhibitory pair formed by glutamate & GABA in the brain. Interestingly, the two exitatory amino acids -- glutamic acid & aspartic acid -- are the two acidic amino acids found in proteins, insofar as both have two carboxyl groups rather than one.
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VI. GLUTAMIC ACID (GLUTAMATE)
Glutamate Glutamate
Glutamate is the most common neurotransmitter in the brain. It is always excitatory, usually due to simple receptors that increase the flow of positive ions by opening ion-channels. Glutamate stimulation is terminated by a (chloride-independent) membrane transport system that is only used for re-absorbing glutamate & aspartate across the pre-synaptic membrane. Glutamate & aspartate re-enter the cell by a transporter driven by the high extracellular concentrations of Na+ and the high intracellular concentrations of K+. Soduim enters the cell along with the amino acids and potassium leaves the cell -- much the way a pulley couples the lifting of a light weight with the fall of a heavier weight. Thus, glutamate/asparate entry is indirectly powered by the ATP-driven Na+-K+-ase (sodium pump) which creates the high ion concentration gradients.
Possibly the most complicated of all neurotransmitter receptors is the NMDA glutamate receptor. N-Methyl-D-Aspartate is a synthetic chemical not naturally found in biological systems, but it binds specifically to the NMDA glutamate receptor (receptors are frequently named for artificial substances that bind to the receptor with higher specificity than their natural neurotransmitter ligands). The NMDA receptor is the only known receptor which is regulated both by a ligand (glutamate) and by voltage. There are at least 5 binding sites which regulate NMDA receptor activity, ie, sites for (1) glutamate (2) glycine (3) magnesium (4) zinc and (5) a site that binds the hallucinogenic substance phencyclidine (PCP, "angel dust"). Phencyclidine can induce psychosis -- an NMDA effect that is difficult to explain. NMDA receptors have a capacity for an activity-dependent increase in synaptic efficiency known as LTP (Long-Term Potentiation), which may be crucial to some forms of learning & memory. Inhibition of NMDA activity (and LTP) is believed to be an important part of the way ethanol affects brain functions.
NMDA receptors are most densely concentrated in the cerebral cortex (hippocampus, especially -- particularly the CA1 region), amygdala, & basal ganglia. They are particularly vulnerable to glutamic acid excitotoxicity, ie, damaging effects due to excessive excitatory neurotransmitter release. Both aspartic acid & glutamic acid (the two amino acids having 2 carboxyl groups -- the "acidic amino acids") have the capacity for destroying neurons when released in excessive amounts (although calcium seems to be more of a cause than acidity). Monosodium glutamate (MSG), a major component of soya sauce, has been shown to destroy nerve cells when fed to young animals. Insofar as glutamate does not normally cross the blood-brain barrier, it is open to question whether this is relevant to a human adult. Increased alertness (or anxiety) due to caffeine may be mainly due to blockage of adenosine receptors which normally inhibit glutamate release.
Glutamate released into synapses is either reabsorbed directly into neurons by the ion-exchange transport system described above, or is soaked-up by astrocytes (glial cells) which convert the glutamate into glutamine (a molecule which cannot cause excitotoxicity). The glutamine can then be safely transported back to neurons for re-conversion into glutamate. One of the damaging effects of mercury poisoning is swelling of astrocytes, which are rendered unable to soak-up glutamine from synapses (contributing to excitotoxicity). Excitotoxicity due to glutamic acid is a major destructive process seen in stokes and other forms of brain ischemia (see Ischemia and Reperfusion Injury in Cryonics).
Nitric oxide can act as neuromodulator when glutamate stimulation of NMDA receptors results in nitric oxide synthesis & release -- enhancing neurotransmitter release from adjacent synapses. Granule cells of the dentate gyrus of the hippocampus are rich in nitric oxide synthetase. Nitric oxide may contribute to LTP.
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VII. GAMMA AMINO BUTYRIC ACID (GABA)
GABA Biochemistry [GABA Biochemistry]
GABA is the major inhibitory neurotransmitter of the brain, occurring in 30-40% of all synapses (second only to glutamate as a major brain neurotransmitter). It is most highly concentrated in the substantia nigra & globus pallidus nuclei of the basal ganglia, followed by the hypothalamus, the periaqueductal grey matter ("central grey") and the hippocampus. The GABA concentration in the brain is 200-1000 times greater than that of the monoamines or acetylcholine.
GABA is somewhat unique among neurotransmitters insofar as it is commonly inactivated (after release into the synapse) by active transport into the astrocyte glial cells that are closely associated with synapses. Both glutamate and GABA are synthesized in the brain from the Krebs citric acid molecule alpha-keto glutarate -- a reaction known as the "GABA shunt". GABA is synthesized from glutamic acid and is catabolized back into the citric acid cycle. The vitamin B6 derivative pyridoxal phosphate is a cofactor in the synthesis of GABA, which is why seizures occur in Vitamin B6 deficiency. GABA levels rise when the citric acid cycle activity is low (ie, when cell energy usage is low), and the resultant generalized GABA inhibitory effect on the brain neurons can be protective during hypoxia or ischemia.
Like glycine, the GABA receptor is connected to a chloride ion channel, allowing more chloride ion to enter the cell and thus making the membrane less likely to depolarize. A closely associated receptor site will bind to benzodiazepines (such as diazepam) to increase the frequency of channel opening. Caffeine can neutralize the effects of benzodiazepine tranquilizers such as diazepam (Valium®). Benzodiazepines act by enhancing the effect of GABA on GABAA receptors, whereas caffeine has an opposite effect by inhibiting GABA release. Barbiturates slightly decrease the frequency of opening, but prolong the duration. The benzodiazepine receptor site is thought to be the natural site of action of a yet-unidentified peptide. By potentiating the effects of GABA, the benzodiazepines function as so-called "minor tranquilizers" (to be distinguished from the anti-psychotic "major tranquilizers"). Anxiety is the most frequently diagnosed psychiatric disorder -- affecting 10-30% of people -- which is why diazepam (Valium) was for many years the most frequently prescribed drug in North America. Alcohol & barbiturates have similar effects on the GABA receptor. In fact, potentiation of chloride influx into neurons is a major mechanism in the effect of ethanol on the brain. Some of the effects of benzodiazepines are probably due to GABA synapses on monoamine-producing neurons. GABA receptors can also be blocked, and the insecticide dieldrin is used for this purpose.
Prolonged use of benzodiazepines results in adaptation of the receptors to their use. Receptors may increase in number and/or sensitivity to GABA. (An increase or decrease in receptor number or sensitivity due to receptor alteration by drugs is known as upregulation or downregulation, respectively. A larger dose of benzodiazepine may be needed to produce the same result -- a phenomenon known as tolerance. Withdrawal of the drug can result in GABA receptor hypoactivity producing symptoms worse than the ones that the patient originally sought treatment for. Such symptoms are called withdrawal. The phenomenon of receptor adaptation and drug dependence is seen with most drugs that act at synapses, including ones that are excitatory or potentiating as well as inhibitory or deactivating.
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VIII. ACETYLCHOLINE
Acetylcholine Acetylcholine
Acetylcholine was the first neurotransmitter discovered and is the major neurotransmitter in the peripheral nervous system (the only other peripheral neurotransmitter being norepinephrine). Acetylcholine is usually (but not always) an exitatory neurotransmitter -- in contrast to the monoamine neurotransmitters, which are nearly always (with a few exceptions) inhibitory. Acetylcholine in the brain is produced from acetyl-CoA, resulting from glucose metabolism, and from choline, which is actively transported across the blood-brain barrier. Most dietary choline comes from phosphatidyl choline, the major phospholipid in the membranes of plants&animals (but not bacteria). The acetyl-CoA & choline are independently synthesized in the neuron cell body and independently transported along the axon to the synapse where they are conjugated into acetylcholine.
There are comparatively few acetylcholine receptors in the brain, but outside the brain acetylcholine is the major neurotransmitter controlling the muscles. Body muscles can be divided into the skeletal muscles system (under voluntary control) and the smooth muscles of the autonomic nervous system (controlling heart, stomach, etc. -- not under voluntary control). The autonomic nervous system is further subdivided into sympathetic and parasympathetic divisions. Direct innervation of skeletal muscles is due to acetylcholine, as is the innervation of smooth muscles of the parasympathetic nervous system. Direct innervation of the sympathetic nervous system (except for sweat glands) is due to norepinephrine (or both epinephrine & norepinephrine in the case of the adrenal medulla).
Sympathetic and Parasympathetic Nervous Systems [Sympathetic and Parasympathetic Nervous Systems]
The sympathetic nervous system innervates body organs in "fight or flight" situations, so the role of norepinephrine as the end-organ neurotransmitter should not be surprising. End-organ stimulation by acetylcholine in the parasympathetic nervous system is more "vegetative", eg, assisting digestion. Acetylcholine receptors are of two types: (1) a fast-acting ion-channel controlled receptor and (2) a slow-acting receptor that acts through a G-protein (Guanine nucleotide-binding protein) that stimulates second-messengers (often cyclic AMP) to indirectly open ion-channels. Direct ion-channel controlling receptors can respond in microseconds, whereas indirect second-messenger controlling receptors take milliseconds to produce a response. Only indirect, second-messenger controlling receptors have the capacity for plasticity. The two acetylcholine receptor classes are named for artificial toxins that selectively activate them. The fast-acting receptor is named nicotinic, because it is specifically activated by the toxin found in tobacco. The slow-acting receptor is named muscarinic, because the toxin muscarine (found in poisonous mushrooms) and acetylcholine will activate it, but nicotine will not.
Parasympathetic nerves are either cranial or sacral. 75% of all parasympathetic fibers arise from a single cranial nerve: the vagus nerve. These fibers travel to end-organs containing ganglia. It is the short postganglionic nerves from the ganglia to the smooth muscles in the end-organs which are muscarinic. The preganglionic fibers are nicotinic. Similarly, the preganglionic fibers of the sympathetic nervous system are nicotinic, although the sympathetic ganglia exist as distinct nodules closer to the spinal cord. The neuromuscular junction of skeletal muscles is also nicotinic.
Considering the rapidity with which skeletal muscles must often be able to respond to the volition to move, it is understandable that they are controlled by fast-acting nicotinic receptors. Unlike other neurotransmitters (which rely on re-uptake), acetylcholine activity in both muscarinic and nicotinic synapses is primarily stopped by an enzyme, ie, acetylcholinesterase. For nicotinic synapses, this means that a signal can be both rapidly initiated and rapidly terminated. The choline resulting from the hydrolysis of acetylcholine can be transported across the presynaptic membrane for resynthesis into acetylcholine.
Some snake venoms contain toxins that block nicotinic receptors, thereby paralyzing their victims. Similarly, some South American Indians used the nicotinic blocking agent curare (extracted from plants) as a poison on their arrowheads. Atropine, which blocks muscarinic receptors, is also a poison. But atropine-like substances are of use for dilating the eye through topical application, for examination of the retina.
[cholinergic pathways in the brain]
Not only are there relatively few cholinergic neurons in the brain, but their distribution is "spotty" -- in contrast to the monoamines which have distinct midbrain nuclei serving as the major sources of brain innervation. Most brain cholinergic receptors are muscarinic, which may make sense insofar as only second-messenger controlled receptors are capable of synaptic plasticity. The site of greatest acetylcholine synthesis in the brain is the interpeduncular nucleus (located near the substantia nigra in the midbrain). All of the interneurons in the striatum (caudate nucleus & putamen of the basal ganglia) and the nucleus accumbens are cholinergic. The septum provides cholinergic fibers to the septal-hippocampal tract. The primary cholinergic input to the cerebral cortex comes from the basal nucleus of Meynert, which is the most prominent structure in the substantia innominata (ventral to the anterior half of the globus pallidus, and adjacent to the hypothalamus). Meynert's nucleus also innervates the basolateral amygdala, the basal ganglia and the reticular nucleus of the thalamus. Cholinergic input from the basal nucleus to the cerebral cortex is active in both the waking state and in REM sleep, but is reduced in non-REM sleep.
Administration of centrally-acting muscarinic blocking agents results in memory loss for normal individuals. The fact that Alzheimer's Disease patients show severe reduction in Meynert's nucleus neurons has led to the suspicion that cholinergic loss could be an important factor in memory loss for these patients. Benefits from the anticholinesterase drugs have reinforced this belief. But Alzheimer's patients have neurofibrillary tangles, loss of NMDA receptors and reduced numbers of noradrenergic & serotonergic neurons as well. Some Alzheimer's patients show normal cholinergic cell numbers in Meynert's nucleus.
Centrally-acting anticholinesterases such as physostigmine (which can cross the blood-brain barrier -- in contrast to neostigmine, which cannot) will worsen the tremors seen in Parkinson's Disease. Conversely, atropine-like substances (which are anti-muscarinic) reduce those tremors. These effects are clearly a consequence of the cholinergic interneurons in the striatum. Physostigmine & neostigmine are known as reversible anticholinesterases because they bind to acetylcholinesterase, but will eventually disengage. This makes them of therapeutic use for glaucoma & myasthenia gravis. Irreversible anticholinesterases which permanently bind-to and inactivate acetylcholinesterase, are only of use as insecticides. The only treatment for poisoning by these substances is atropinic drugs.
Stimulation of brain nicotinic receptors by nicotine from tobacco and arecoline from betal nuts (chewed by a quarter of the population of India) is a source of euphoric addiction for a large segment of the world's population. Research funded by the tobacco industry has shown that working memory may be improved by nicotinic stimulation of dopaminergic neurons in the substantia nigra & ventral tegmental area [BRAIN RESEARCH 657:165-170 (1994)] and that nicotine may be able to improve learning & memory in Alzheimer's patients showing a loss of nicotinic receptors in the neocortex & hippocampus [PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR 52:517-523 (1995)].
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IX. DOPAMINE
The primary monoamine neurotransmitters are dopamine, norepinephrine and serotonin. Dopamine and norepinephrine are catecholeamines, whereas serotonin is an indolamine.
The amino acid tyrosine is not an essential amino acid because it can be synthesized in the liver from phenylalanine by the enzyme phenylalanine hydroxylase. But it cannot be synthesized in the brain, and therefore must enter the brain by the large neutral amino acid transporter, which also transports phenylalanine, tryptophan, methionine and the branch-chained amino acids. These amino acids all compete for the transporter, so a large quantity of one of the other amino acids in the blood stream could greatly limit the amount of tyrosine entering the brain. One case in which this occurs is when there is a liver deficiency of phenylalanine hydroxylase. In that case, Phenylalanine reaches high concentrations in the blood and monopolizes the large neutral amino acid transporter, producing the mental retardation of phenylketonuria.
Dopamine synthesis [Dopamine synthesis]
Once in the brain, tyrosine can be converted to DihydrOxyPhenylAlanine (DOPA) by the tyrosine hydroxylase enzyme using oxygen, iron and TetraHydroBiopterin (THB) as co-factors. High concentrations of dopamine inhibit tyrosine hydroxylase activity through an influence on the THB co-factor. DOPA is converted to dopamine by Aromatic Amino Acid Decarboxylase (which is fairly nonspecific insofar as it will decarboxylate any aromatic amino acid) using PyridoxaL Phosphate (PLP) as a co-factor. This reaction is virtually instantaneous unless there is a Vitamin B6 deficiency.
Dopamine & epinephrine are primarily inhibitory neurotransmitters that produce arousal. This may sound paradoxical, but the most likely explanation for this effect is that the postsynaptic cells for catecholamines themselves are inhibitory. There are 3-4 times more dopaminergic cells in the CNS than adrenergic cells. Dopamine in the caudate nucleus facilitates posture, whereas dopamine in the nucleus accumbens is associated with an animal's speed (and pleasure).
[dopamine receptors]
There are two primary dopamine receptor-types: D1 (stimulatory) and D2 (inhibitory), both of which act through G-proteins. D2 receptors often occur on the dopaminergic neurons, partially for the purpose of providing negative feedback. These so-called autoreceptors can inhibit both dopamine synthesis and release.
The binding of dopamine to D1-receptors stimulates the activity of Adenylyl Cyclase (AC), which converts ATP to cyclic AMP (cAMP), a second messenger which binds to Protein Kinase A (PKA). PKA then modulates the activity of various proteins by the addition of phosphate.
[dopamine pathways]
There are 4 main dopaminergic tracts in the brain: (1) the nigrostriatial tract from the substantia nigra to the striatum accounts for most of the brain's dopamine (2) the tuberoinfundibular tract from the arcuate nucleus of the hypothalamus to the pituitary stalk, which has a controlling effect on the release of the hormones prolactin through tonic inhibition via D2 receptors (3) the mesolimbic tract from the ventral tegmental area to many parts of the limbic system and (4) the mesocortical tract from the ventral tegmental area to the neocortex, particularly the prefrontal area. Dopamine cells project topographically to the areas they innervate.
[monoamine metabolism]
Both dopamine & norepinephrine are catabolized by a two-step process involving the enzymes MonoAmineOxidase (MAO) and Catechol-O-MethylTransferase (COMT). COMT is primarily active in the synapses, and uses &S-Adenosyl Methionine (SAM) as a methyl-group donor. MAO is primarily active in the pre-synaptic terminal against catecholamines that are not safely enclosed in storage vesicles. Normally, COMT only catabolizes about 10% of synaptic catecholamine, since catecholamine synaptic activity is primarily terminated by re-uptake into the pre-synaptic neuron terminal. MAO accounts for a much larger portion of catecholamine metabolism.
The darkly pigmented neurons in the pars compacta of the substantia nigra accounts for 80% of the dopamine in the brain. The dark pigment neuromelanin is a dopamine polymer that makes the substantia nigra appear black. Motor control in the striatum (caudate nucleus and putamen) is thought to involve a balance between inhibitory dopaminergic (D2) and excitatory cholinergic neurons.
A form of MAO, known as MAO-B, is the most common form of MAO in the striatum. MAO-B is known to metabolize the neurotoxin MPTP to its active form. When striatum dopamine is depleted to 20% the original level, symptoms of Parkinson's Disease appear. Administration of DOPA is the most common treatment. The monoamine oxidase inhibitor deprenyl will specifically inhibit MAO-B, thereby making deprenyl a useful adjunct to DOPA therapy. The ergot derivative bromocriptine is a D2 agonist which can alleviate the symptoms. (Deprenyl's reputed anti-aging capabilities may be related to MAO-B inhibition. Similarly, carnosine, which has been shown to reduce cellular senescence, inhibits MAO-B.)
Phenothiazine derivatives [Phenothiazine derivatives]
Schizophrenia is thought to be due to an overstimulation of D2 receptors in the mesolimbic and mesocortical systems. Evidence for the "excess dopamine" theory of schizophrenia comes largely from the fact that D2 antagonist drugs alleviate the symptoms, whereas substances which increase D2 stimulation, such as amphetamines, can induce psychotic symptoms (which are reversible with D2 antagonists). About 10% of Parkinsonian patients given DOPA treatment will develop psychotic symptoms resembling schizophrenia.
The major classes of antipsychotic drugs are the phenothiazines (eg, chlorpromazine), the butyrophenones (eg, haloperidol) and the thioxanthenes (eg, chlorprothixene). Butyrophenones are 100 times more potent against D2 receptors than against D1 receptors. The similarity in shape between a portion of the chlorpromazine molecule and dopamine indicates how chlorpromazine could bind to a dopamine receptor without triggering a response.
The mesolimbic & mesocortical dopaminergic systems are thought to play an important role in motivation, by attaching cognition of incentive significance to stimuli. In experiments on animals that are motivated to electrically self-stimulate themselves with electrodes implanted in their brains, dopamine is the mediating neurotransmitter for the locus ceruleus, lateral hypothalamus, ventral tegmental area and sulcal prefrontal cortex (but not the nucleus accumbens or substantia nigra).
Cocaine particularly increases dopaminergic activity in the mesolimbic areas of the brain by inhibiting dopamine re-uptake in the ventral tegmental area and the nucleus accumbens. Amphetamine seems more generalized in its action, not only by inhibiting re-uptake, but by releasing dopamine from most brain regions. Both cocaine & amphetamine produce feelings of psychological energy & arousal, associated with diminished appetite & need for sleep. Both cocaine & amphetamine can lead to visual & tactile hallucinations as well as paranoid thinking, although the psychotic effects of amphetamine may also be mediated by increased serotonin release. Chronic amphetamine users seem to lose a capacity for normal pleasure -- which has been correlated with neuron degeneration in the mesolimbic area.
Perception of time-intervals is believed to be mediated by spiny neurons located in the striatum of the basal ganglia. Timing begins with a burst of dopamine and ends with a recognized signal. Marijuana slows subjective time by lowering dopamine available, whereas cocaine and methamphetamine accelerates the sense of time by increasing dopamine availability. (Adrenaline and stress hormones can also "make seconds feel like hours".)
The natural brain amine phenylethylamine (PEA, found in chocolate) has been associated with the "love-excitement" of sexual attraction & emotional infatuation.
PEA concentrations are normally highest in the nucleus accumbens (a "reward center")followed by the frontal & cingulate cortices. Levels spike during orgasm and ovulation. PEA is very similar to amphetamine in chemical structure and may likewise act by causing dopamine release, but endorphin release may be a significant effect. PEA is preferentially oxidized by MonoAmine Oxidase-B (MAO-B), which may account for the anti-depressant effects of selegiline.
Other actions of dopamine include the induction of vomiting by stimulation of D2 cells in the chemoreceptor trigger zone, stimulation of growth hormone release by D2 receptors, and increased exploration & locomotion (thought to be connected to dopaminergic activity in the nucleus accumbens). Sexual behavior in the male is increased by dopamine agonists, whereas sexual behavior in the female is increased by dopamine antagonists.
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X. NOREPINEPHRINE (NORADRENALIN)
Noradrenalin Synthesis from Dopamine Noradrenalin Synthesis from Dopamine
Norepinephrine (along with acetylcholine) is one of the two neurotransmitters in the peripheral nervous system. Norepinephrine is synthesized from dopamine by means of the enzyme Dopamine Beta-Hydroxylase (DBH), with oxygen, copper and Vitamin C as co-factors. Dopamine is synthesized in the cytoplasm, but norepinephrine is synthesized in the neurotransmitter storage vesicles. Cells that use norepinephrine for formation of epinephrine use SAMe (S-AdenylMethionine) as a methyl group donor. Levels of epinephrine in the CNS are only about 10% of the levels of norepinephrine.
The most prominent noradrenergic (ie, norepinephrine-containing) nucleus is the locus ceruleus in the pons, which account for over 40% of noradrenergic neurons in the rat brain. Most of the other noradrenergic neurons are clustered in a region described as the lateral tegmental area. The neocortex, hippocampus, and cerebellum receive noradrenergic stimulation exclusively from the locus ceruleus. Most of the dopaminergic innervation of the hypothalamus comes from the lateral tegmental nuclei.
[noradrenergic pathways in the brain]
Electrical stimulation of the locus ceruleus produces a state of heightened arousal. The noradrenergic system is most active in the awake state, and it seems to be important for focused attention, in contrast to the motor arousal of dopamine. Although the locus ceruleus has been identified as a pleasure center, it also seems to contribute to anxiety. Increased neuronal activity of the locus ceruleus is seen upon the occurrence of unexpected sensory events. Brain norepinephrine turnover is increased in conditions of stress. Benzodiazepines, the primary antianxiety drugs, decrease firing in the locus ceruleus, thus reducing distribution of noradrenalin to the forebrain and amygdala. This is part of the explanation for the use of benzodiazepines for inducing sleep.
Active projection of norepinephrine from the locus coeruleus of the reticular activating system to the forebrain is a key feature of awakeness-arousal as distinguished from sleep. Norepineprhine projection to the basal nucleus of the forebrain is low in sleep -- virtually absent in REM (Rapid Eye-Movement) sleep. The basal nucleus when stimulated by norepinephrine from the locus coeruleus sends neuromodulating acetylcholine to the cerebral cortex, thereby promoting alertness.
The beta-adrenergic blocking drug propranolol has also been used to treat anxiety. By blocking the adrenergic inputs to the amygdala, beta-blockers inhibit the formation of traumatic memories. Cortisol stimulation of the locus coeruleus due to chronic stress exacerbates norepinephrine stimulation of the amygdala.
Beta-noradrenergic receptors also apparently inhibit feeding, whereas alpha-receptors seem to stimulate feeding.
Although MAO inhibitors reduce metabolism of all catecholamines, it is believed that the anti-depressant effect is more related to norepinephrine than to dopamine. Most MAO in the brain is of type-B, but drugs selective for inhibiting MAO-A have proven to be better anti-depressants. MAO-A preferentially metabolizes norepinephrine & serotonin. MAO-A inhibiting drugs given for depression have critically elevated blood pressure in patients eating tyramine-containing foods (such as cheese) due to the failure to metabolize tyramine (which can act as a pressor agent). These drugs (eg, phenelzine & pargyline) inactivate MAO by forming irreversible covalent bonds. More modern MAO inhibitors are safer because they form reversible bonds. MAO-B inhibitors like deprenyl are also less likely to cause the "cheese effect". (Alcohol also selectively inhibits MAO-B.)
Tricyclic Antidepressants Tricyclic Antidepressants
Tricyclic anti-depressants derive their name from their 3-ring structure. Desipramine only inhibits norepinephrine re-uptake, with little effect on dopamine. Imipramine & amitriptyline are inhibitors of norepinephrine and serotonin re-uptake by the presynaptic terminals, but are more potent for serotonin. Cocaine is also a potent inhibitor of catecholamine re-uptake, but it does not act as an anti-depressant. Weight gain due to increased appetite is a frequent side effect of tricyclic anti-depressants, particularly of amitrip- tyline. By contrast, both cocaine & amphetamine reduce appetite.
Both MAO inhibitors and tricyclic anti-depressants have immediate effects on brain monoamines, but clinically anti-depressants require several weeks of administration before they produce a therapeutic effect. It is therefore believed that it is not the immediate effects on neurotransmitters that is producing the antidepression, but the long-term effects on modification of receptors.
Excessive cortisol secretion is seen in 40-60% of depressed patients, associated with diminished noradrenergic inhibition of corticotropin-releasing hormone secretion in the hypothalamus. Corticotropin-releasing hormone induces anxiety in experimental animals.
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XI. SEROTONIN (5-HYDROXYTRYPTAMINE, 5-HT)
[indole molecule]
Serotonin was isolated from the blood serum as a substance causing powerful smooth muscle contraction. Only later was it demonstrated to be tryptamine with a hydroxyl group at the 5-position. Only 1-2% of the serotonin in the body is in the brain, insofar as serotonin is widely distributed in platelets, mast cells, etc. But there is no equilibration between body serotonin and brain serotonin -- the serotonin in the brain is independently synthesized from tryptophan transported across the blood-brain barrier.
Serotonin synthesis [Serotonin synthesis]
Serotonin synthesis is a 2-step process, the first step of which requires the enzyme tryptophan hydroxylase with oxygen, iron and THB as co-factors. Neither the enzyme nor the co-factors are rate-limiting for either step of these reactions -- virtually all brain tryptophan is converted to serotonin. Serotonin concentration in the brain is far more sensitive to the effects of diet than any other monoamine neurotransmitter -- and can be increased up to 10-fold by dietary supplementation in laboratory animals.
Consumption of a meal that is high in carbohydrate, branch-chained amino acids and tryptophan has a particularly dramatic effect because both glucose from carbohydrate and branch-chained amino acids (especially leucine) increase insulin secretion. Insulin facilitates the transport of the branch-chained amino acids into muscle cells, thereby reducing the competition tryptophan faces for the large neutral amino acid transporter that takes it across the blood-brain barrier. The resultant drowsiness induced by serotonin is a common effect of a large carbohydrate meal.
Melatonin [Melatonin]
The richest concentration of serotonin in the body can be found in the pineal body, even though this gland does not use serotonin as a transmitter. Instead, serotonin is primarily used for synthesis of melatonin, so-called because it can darken the skin of amphibians ("melas" is Greek for "black") -- although it has also been reported to induce pigment lightening in cells. Melatonin is synthesized from serotonin in a 2-step process that takes an acetyl group from acetyl-CoA and a methyl group from SAMe (S-AdenosylMethionine).
Melatonin is of particular importance for regulating diurnal (circadian) & seasonal behavior & physiology in mammals. The pineal body has been called a "third eye" because its activity is influenced by light. In mammals, noradrenergic neurons near the optic nerve are inhibited by light. In darkness, norepinephrine stimulation of pineal cells causes the release of cyclic AMP second-messenger, which activates (phosphorylates) the N-acetyl transferase enzyme which catalyzes acetylation of serotonin. In many specied (including humans) melatonin is an inhibitor of sexual activity in both sexes. Decreased melatonin in the Spring leads to rutting -- and the birth of offspring in the warmer seasons. Melatonin also stimulates production of brown adipose tissue, a special form of fat which (when burned) only produces heat, not ATP. This is especially important for hibernating animals.
[serotonin pathways in the brain]
Serotonin neurotransmitter neurons are located in the raphe nuclei. The caudal (closer to the "tail") nucleus projects largely to the medulla and spinal cord for the regulation of pain perception. The rostral (closer to the "beak") nucleus projects extensively to the limbic structures and the cerebral cortex. In the limbic system, especially, the projections are co-localized with norepinephrine receptors -- and the two transmitters seem to work in conjunction in the regulation of arousal.
The tricyclic antidepressants typically inhibit both norepinephrine & serotonin re-uptake by pre-synaptic terminals. The effectiveness of these neurotransmitters against depression seems to be due to both decreased functional activity of beta-postsynaptic norepinephrine receptors and increased activity of type−2 serotonin receptors in the limbic regions of the brain. But experimental depletion of monoamines only leads to depression in subjects having a family history of this disorder [MOLECULAR PSYCHIATRY; Ruhe,HG; 12(4):331-359 (2007)].
The SupraChiasmatic Nucleus (SCN) of the hypothalamus regulates the mammalian circadian clock ("day-night cycles"), partially in response to light. Melatonin release is inhibited as a result of the response of the SCN to light. The SCN is richly innervated by serotonergic input from the dorsal raphe nucleus. Serotonin inhibits the responsiveness of the SCN (and thus the circadian rhythm) to light [ANNALS OF MEDICINE 31:12-33 (1999)]. Sleep deprivation increases serotonin release in the SCN [BRAIN RESEARCH 909:81-91 (2001)]. With aging there is a decline in both serotonin transporters [LIFE SCIENCES; Yamamoto,M; 71(7):751-757 (2002)] and serotonin receptors [NEUROPSYCHOPHARMACOLOGY; Meltzer,MD; 71(7):751-757 (2002)]. Depletion of serotonin is believed to be related to the disruption of the circadian rhythm associated with senescence [AMERICAN JOURNAL OF PHYSIOLOGY 272(2 Pt 2):R509-R513 (1997)].
As little as one or two grams of L−tryptophan is effective in decreasing sleep latency time [PSYCHOPHARMACOLOGY; Schneider-Helmert,D; 89(1):1-7 (1986) and PHARMACOPSYCHIATRY; Demisch,K; 20(6):242-244 (1987)]. L−tryptophan either improves or has not effect on other sleep parameters, with the exception of a suppressive effect on REM sleep [EUROPEAN NEUROLOGY; Korner,E; 25(Suppl 2):75-81 (1986)].
Serotonin seems to have distinctive actions contributing to anxiety and impulsive behavior. Patients with evidence of low serotonin levels have attempted suicide by very dramatic means, such as cutting the throat. This may explain some of the therapeutic effects of fluoxetine (Prozac), which selectively prevents the re-uptake of serotonin. Fluoxetine is also distinctive because it has a half-life of about four days. Fluoxetine has been used therapeutically for panic, obsessive-compulsive and eating disorders (such as bulimia). Unlike the tricyclic anti-depressants, which often stimulate appetite, fluoxetine more often reduces appetite. Fluoxetine may even enhance learning [PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR 52:341-346 (1995)]. Depression patients treated with tryptophan as well as fluoxetine show less sleep disturbance at the outset of treatment than patients treated with fluoxetine alone [JOURNAL OF PSYCHIATRY & NEUROSCIENCE; Levitan,RD; 25(4):337-346 (2000)].
Monkeys with high levels of testosterone & low levels of serotonin are both aggressive & lacking in restraints on impulsive/violent behavior. Arsonists who commit their crime for mercenary reasons show normal levels of serotonin, but those who commit the crime impulsively have low serotonin. Lead interferes with serotonin synapse formation. Monkeys experimentally exposed to lead became so dangerously aggressive that the study was halted early [CHEMICAL & ENGINEERING NEWS 81(22):33-37 (2003)].
Reserpine prevents the transport of all the monoamines (and acetylcholine) into storage vesicles in the presynaptic membrane -- leaving them vulnerable to destruction by monoamine oxidase. Reserpine (as extracts from the Rauwolfia plant) was used for centuries in India to treat "hysteria". Reserpine has been used as a potent tranquilizer, but it can produce serious depression that may lead to suicide attempts.
LySergic acid Diethylamine (LSD) acts most strongly on the type-2 serotonin receptors, but it also has some effect on norepinephrine receptors. Serotonin seems to play a role in dreaming. During both dreaming and LSD intoxication, electrical activity in the visual cortex arises from the brain stem rather than from the eyes. LSD not only induces visual hallucinations, but it heightens sensory awareness while diminishing control of sensory input. The reduced ability to distinguish between sensory impressions can lead to feelings of being "in union with the universe". Artificial stimulation of the raphe simulates the actions of LSD, decreasing habituation to repetitive stimuli. Low doses of LSD & amphetamine, however, have been shown to enhance a form of associative learning.
High-estrogen contraceptives may have contributed to depression by lowering serotonin levels in the brain. Low levels of growth hormone in depressed patients may be due either to low levels of norepinephrine, serotonin, or both.
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XII. PEPTIDES
Peptides are the most common neurotransmitters in the hypothalamus. Their complex structure can allow for high receptor specificity. They are all synthesized on ribosomes and are all inactivated by hydrolysis at the synapse (rather than by re-uptake). Peptides are far more potent than other neurotransmitters, requiring only very small amounts to produce a profound effect. Even very minute amounts of somatostatin can inhibit growth hormone release.
Opioid peptides include the endorphins, enkephalins and dynorphins. Enkephalins are frequently found in presynaptic (axo-axonic) synapses. Opiates and enkephalins (or endorphins) inhibit the firing of locus ceruleus neurons. The highest concentration of opioid receptors are found in the sensory, limbic and hypothalamic regions of the brain -- and are particularly high in the amygdala & periaqueductal grey area. Opioids tend to be released as slower-acting co-transmitters which modulate the action of the associated neurotransmitter (such as glutamate) which is being released from the same synapse. Although opioids are generally inhibitory, they have an excitatory effect on hippocampal pyrimidal neurons mediated by inhibition of GABA release.
Cholecystokinin (CCK) seems to function in the production of satiety. Injection of small quantities of this peptide into the ventricles or the paraventricular nucleus can inhibit feeding. CCK is associated with dopamine synapses in some limbic areas, and appears to modulate dopamine release. Such peptide synergy with other transmitters is common. For example, GABA is often associated with somatostatin and serotonin with Substance P.
Low doses of the peptide vasopressin have been shown to enhance learning in laboratory animals. However, humans with vasopressin deficiency show no signs of memory impairment. Because vasopressin is potent in increasing blood pressure, its use by humans should be approached with caution. Safer analogues may yet be found.
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XIII. RELEVANCE TO CRYONICS
The profound effects of neurotransmitters on the human psyche seems to portend substantial implications for personal identity. But their obvious emphemeral nature makes it seem unlikely that they can be described as being part of "the anatomical basis of mind". Water is also an important component of the human brain, but water is very uniform and replaceable. Preservation of the means of producing, storing, releasing and re-uptaking neurotransmitters (ie, the receptors and synaptic connections) seems more important than preserving the neurotransmitters themselves. The fact that anti-depressants & anti-psychotics take weeks to become effective may offer some clue in this regard.
In a sense, however, many of the "structural" features of neurons are no less ephemeral than neurotransmitters. They can be produced or replaced by enzymes coded-for by DNA in much the same way as neurotransmitters. This would seem to point to neuron gene expression as the key locus for identity, and the most crucial site for preservation. But gene expression is determined by the mileu of the neuron -- a circular homeostasis that seemingly does not allow for finding "ultimate causes". Moreover, considering the demonstrably critical role played by astrocytes in GABA re-uptake at synapses, one might wonder whether glial cells are also an essential component of identity.
